PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
33810025-17	2021	Subsequently, the strengths of interaction energies between ibrutinib and its interacting residues in tyrosine kinase BTK were quantified by means of the double hybrid DFT method B2PLYP.	ibrutinib	60-69	Bruton tyrosine kinase	Homo sapiens	118-121
33761747-6	2021	In the context of the BTK inhibitor ibrutinib, these electrophiles showed lower intrinsic thiol reactivity than the unsubstituted ibrutinib acrylamide.	ibrutinib	36-45	Bruton tyrosine kinase	Homo sapiens	22-25
33761747-6	2021	In the context of the BTK inhibitor ibrutinib, these electrophiles showed lower intrinsic thiol reactivity than the unsubstituted ibrutinib acrylamide.	ibrutinib	130-139	Bruton tyrosine kinase	Homo sapiens	22-25
33942495-8	2021	Both were treated off-label with the first-generation Bruton"s tyrosine kinase inhibitor ibrutinib for 12 months.	ibrutinib	89-98	Bruton tyrosine kinase	Homo sapiens	54-78
33807411-4	2021	Novel covalent kinase inhibitors, such as the clinically approved BTK inhibitor ibrutinib (IBR) and the preclinical phytochemical withaferin A (WA), have, therefore, gained pharmaceutical interest.	ibrutinib	80-89	Bruton tyrosine kinase	Homo sapiens	66-69
33807411-4	2021	Novel covalent kinase inhibitors, such as the clinically approved BTK inhibitor ibrutinib (IBR) and the preclinical phytochemical withaferin A (WA), have, therefore, gained pharmaceutical interest.	ibrutinib	91-94	Bruton tyrosine kinase	Homo sapiens	66-69
33810025-18	2021	The resulting energetics for the binding of ibrutinib in tyrosine kinase BTK showed that CH-pi interactions and pi-pi stacking interactions between aromatic rings of the drug and hydrophobic residues in its binding pocket dominate the binding interactions.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	73-76
33775465-6	2021	RT-DLBCL on ibrutinib is frequently associated with BTK and PLCG2 mutations.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	52-55
33772839-2	2021	A simple analytical method using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry has been developed and validated for simultaneous quantification of BCR-ABL and Bruton"s tyrosine kinase inhibitors (TKIs) used for chronic leukemia (imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib) in human plasma.	ibrutinib	318-327	ABL proto-oncogene 1, non-receptor tyrosine kinase	Homo sapiens	189-196
33772839-2	2021	A simple analytical method using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry has been developed and validated for simultaneous quantification of BCR-ABL and Bruton"s tyrosine kinase inhibitors (TKIs) used for chronic leukemia (imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib) in human plasma.	ibrutinib	318-327	Bruton tyrosine kinase	Homo sapiens	201-225
33809580-1	2021	The approval of Bruton"s tyrosine kinase (BTK) inhibitors such as ibrutinib and acalabrutinib and the Bcl-2 inhibitor venetoclax have revolutionized the treatment of chronic lymphocytic leukemia (CLL).	ibrutinib	66-75	Bruton tyrosine kinase	Homo sapiens	16-40
33809580-1	2021	The approval of Bruton"s tyrosine kinase (BTK) inhibitors such as ibrutinib and acalabrutinib and the Bcl-2 inhibitor venetoclax have revolutionized the treatment of chronic lymphocytic leukemia (CLL).	ibrutinib	66-75	Bruton tyrosine kinase	Homo sapiens	42-45
33775465-6	2021	RT-DLBCL on ibrutinib is frequently associated with BTK and PLCG2 mutations.	ibrutinib	12-21	phospholipase C gamma 2	Homo sapiens	60-65
33799484-3	2021	The Bruton"s tyrosine kinase inhibitors (BTKi) ibrutinib, acalabrutinib, and zanubrutinib achieve objective responses in the majority of patients as single agent therapy for relapsed MCL, but differ with regard to toxicity profile and dosing schedule.	ibrutinib	47-56	Bruton tyrosine kinase	Homo sapiens	4-28
33806595-2	2021	However, mild bleeding is frequent in patients with B-cell malignancies treated with the irreversible BTKi ibrutinib and the recently approved 2nd generation BTKi acalabrutinib, zanubrutinib and tirabrutinib, and also in volunteers receiving in a phase-1 study the novel irreversible BTKi BI-705564.	ibrutinib	107-116	inhibitor of Bruton tyrosine kinase	Homo sapiens	102-106
33799484-3	2021	The Bruton"s tyrosine kinase inhibitors (BTKi) ibrutinib, acalabrutinib, and zanubrutinib achieve objective responses in the majority of patients as single agent therapy for relapsed MCL, but differ with regard to toxicity profile and dosing schedule.	ibrutinib	47-56	inhibitor of Bruton tyrosine kinase	Homo sapiens	41-45
25371371-0	2015	CXCR4 WHIM-like frameshift and nonsense mutations promote ibrutinib resistance but do not supplant MYD88(L265P) -directed survival signalling in Waldenstrom macroglobulinaemia cells.	ibrutinib	58-67	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
33777941-8	2021	Analysis of the reported AEs suggests that ibrutinib-associated atrial fibrillation is caused by binding to ERBB2/HER2 and ERBB4/HER4.	ibrutinib	43-52	erb-b2 receptor tyrosine kinase 2	Homo sapiens	108-113
33777941-8	2021	Analysis of the reported AEs suggests that ibrutinib-associated atrial fibrillation is caused by binding to ERBB2/HER2 and ERBB4/HER4.	ibrutinib	43-52	erb-b2 receptor tyrosine kinase 2	Homo sapiens	114-118
33777941-8	2021	Analysis of the reported AEs suggests that ibrutinib-associated atrial fibrillation is caused by binding to ERBB2/HER2 and ERBB4/HER4.	ibrutinib	43-52	erb-b2 receptor tyrosine kinase 4	Homo sapiens	123-128
33777941-8	2021	Analysis of the reported AEs suggests that ibrutinib-associated atrial fibrillation is caused by binding to ERBB2/HER2 and ERBB4/HER4.	ibrutinib	43-52	erb-b2 receptor tyrosine kinase 4	Homo sapiens	129-133
29301866-0	2018	Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia.	ibrutinib	59-68	integrin subunit alpha 4	Homo sapiens	44-49
29301866-0	2018	Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia.	ibrutinib	59-68	integrin subunit beta 1	Homo sapiens	50-54
29301866-1	2018	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL).	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
29301866-1	2018	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL).	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
29301866-2	2018	The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments.	ibrutinib	53-62	Bruton tyrosine kinase	Homo sapiens	111-114
29301866-4	2018	In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K.	ibrutinib	21-30	Bruton tyrosine kinase	Homo sapiens	162-165
29301866-5	2018	Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4.	ibrutinib	33-42	integrin subunit alpha 4	Homo sapiens	64-69
29301866-5	2018	Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4.	ibrutinib	33-42	integrin subunit alpha 4	Homo sapiens	256-261
25284608-0	2015	Combination of ibrutinib with ABT-199: synergistic effects on proliferation inhibition and apoptosis in mantle cell lymphoma cells through perturbation of BTK, AKT and BCL2 pathways.	ibrutinib	15-24	Bruton tyrosine kinase	Homo sapiens	155-158
25284608-0	2015	Combination of ibrutinib with ABT-199: synergistic effects on proliferation inhibition and apoptosis in mantle cell lymphoma cells through perturbation of BTK, AKT and BCL2 pathways.	ibrutinib	15-24	AKT serine/threonine kinase 1	Homo sapiens	160-163
25284608-0	2015	Combination of ibrutinib with ABT-199: synergistic effects on proliferation inhibition and apoptosis in mantle cell lymphoma cells through perturbation of BTK, AKT and BCL2 pathways.	ibrutinib	15-24	BCL2 apoptosis regulator	Homo sapiens	168-172
28715249-0	2017	Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor-Modified T Cells After Failure of Ibrutinib.	ibrutinib	148-157	CD19 molecule	Homo sapiens	74-78
28715249-12	2017	Conclusion CD19 CAR-T cells are highly effective in high-risk patients with CLL after they experience treatment failure with ibrutinib therapy.	ibrutinib	125-134	CD19 molecule	Homo sapiens	11-15
25371371-1	2015	CXCR4(WHIM) frameshift and nonsense mutations follow MYD88(L265P) as the most common somatic variants in Waldenstrom Macroglobulinaemia (WM), and impact clinical presentation and ibrutinib response.	ibrutinib	179-188	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
25371371-1	2015	CXCR4(WHIM) frameshift and nonsense mutations follow MYD88(L265P) as the most common somatic variants in Waldenstrom Macroglobulinaemia (WM), and impact clinical presentation and ibrutinib response.	ibrutinib	179-188	MYD88 innate immune signal transduction adaptor	Homo sapiens	53-58
25371371-5	2015	CXCR4(FS) and CXCR4(S338X) cells, but not CXCR4(WT) cells, were rescued from ibrutinib-triggered apoptosis by CXCL12 that was reversed by AKT1, MAPK1 or CXCR4 antagonists.	ibrutinib	77-86	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
24270740-2	2014	Ibrutinib, a BTK inhibitor, has demonstrated a significant clinical activity against chronic lymphocytic leukemia (CLL) in early clinical trials.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-16
24270740-8	2014	Furthermore, activities of BTK and phospholipase Cgamma2 as well as downstream signaling molecules, AKT and ERK, were all coordinately downregulated over time in ibrutinib-treated patients.	ibrutinib	162-171	Bruton tyrosine kinase	Homo sapiens	27-30
25371371-5	2015	CXCR4(FS) and CXCR4(S338X) cells, but not CXCR4(WT) cells, were rescued from ibrutinib-triggered apoptosis by CXCL12 that was reversed by AKT1, MAPK1 or CXCR4 antagonists.	ibrutinib	77-86	C-X-C motif chemokine receptor 4	Homo sapiens	14-19
25371371-5	2015	CXCR4(FS) and CXCR4(S338X) cells, but not CXCR4(WT) cells, were rescued from ibrutinib-triggered apoptosis by CXCL12 that was reversed by AKT1, MAPK1 or CXCR4 antagonists.	ibrutinib	77-86	C-X-C motif chemokine receptor 4	Homo sapiens	14-19
24270740-8	2014	Furthermore, activities of BTK and phospholipase Cgamma2 as well as downstream signaling molecules, AKT and ERK, were all coordinately downregulated over time in ibrutinib-treated patients.	ibrutinib	162-171	AKT serine/threonine kinase 1	Homo sapiens	100-103
25371371-5	2015	CXCR4(FS) and CXCR4(S338X) cells, but not CXCR4(WT) cells, were rescued from ibrutinib-triggered apoptosis by CXCL12 that was reversed by AKT1, MAPK1 or CXCR4 antagonists.	ibrutinib	77-86	C-X-C motif chemokine ligand 12	Homo sapiens	110-116
24270740-8	2014	Furthermore, activities of BTK and phospholipase Cgamma2 as well as downstream signaling molecules, AKT and ERK, were all coordinately downregulated over time in ibrutinib-treated patients.	ibrutinib	162-171	EPH receptor B2	Homo sapiens	108-111
25371371-5	2015	CXCR4(FS) and CXCR4(S338X) cells, but not CXCR4(WT) cells, were rescued from ibrutinib-triggered apoptosis by CXCL12 that was reversed by AKT1, MAPK1 or CXCR4 antagonists.	ibrutinib	77-86	AKT serine/threonine kinase 1	Homo sapiens	138-142
24270740-10	2014	Blocking cell proliferation via inhibition of BTK-mediated signaling may contribute to clinical responses in ibrutinib-treated patients.	ibrutinib	109-118	Bruton tyrosine kinase	Homo sapiens	46-49
25371371-5	2015	CXCR4(FS) and CXCR4(S338X) cells, but not CXCR4(WT) cells, were rescued from ibrutinib-triggered apoptosis by CXCL12 that was reversed by AKT1, MAPK1 or CXCR4 antagonists.	ibrutinib	77-86	mitogen-activated protein kinase 1	Homo sapiens	144-149
25371371-5	2015	CXCR4(FS) and CXCR4(S338X) cells, but not CXCR4(WT) cells, were rescued from ibrutinib-triggered apoptosis by CXCL12 that was reversed by AKT1, MAPK1 or CXCR4 antagonists.	ibrutinib	77-86	C-X-C motif chemokine receptor 4	Homo sapiens	14-19
25371371-7	2015	These studies show a functional role for CXCR4(FS) mutations in WM, and provide a framework for the investigation of CXCR4 antagonists with ibrutinib in CXCR4(WHIM) -mutated WM patients.	ibrutinib	140-149	C-X-C motif chemokine receptor 4	Homo sapiens	117-122
25371371-7	2015	These studies show a functional role for CXCR4(FS) mutations in WM, and provide a framework for the investigation of CXCR4 antagonists with ibrutinib in CXCR4(WHIM) -mutated WM patients.	ibrutinib	140-149	C-X-C motif chemokine receptor 4	Homo sapiens	117-122
34332791-8	2022	In the background of RS, 2/5 patients treated with ibrutinib showed a BTK C481S resistance mutation.	ibrutinib	51-60	Bruton tyrosine kinase	Homo sapiens	70-73
34839996-0	2022	Review of the development of BTK inhibitors in overcoming the clinical limitations of ibrutinib.	ibrutinib	86-95	Bruton tyrosine kinase	Homo sapiens	29-32
34839996-3	2022	Ibrutinib, the first-generation BTK inhibitor, was approved to treat several B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	32-35
34882824-0	2022	Haemorrhagic bullae and purpura associated with the Bruton tyrosine kinase inhibitor ibrutinib.	ibrutinib	85-94	Bruton tyrosine kinase	Homo sapiens	52-74
34732527-8	2022	Furthermore, genes that are differentially expressed in ibrutinib-treated cells are enriched in YAP1 target genes and we showed that ibrutinib, but not acalabrutinib, reduces YAP1 activity in BRAFi-resistant melanoma cells.	ibrutinib	56-65	Yes1 associated transcriptional regulator	Homo sapiens	96-100
34569486-1	2022	INTRODUCTION: Therapy of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with drugs such as ibrutinib and rituximab is often associated with immune suppression, opportunistic infections, and reactivation of virus infections such as hepatitis B virus (HBV).	ibrutinib	110-119	solute carrier family 35 member B2	Homo sapiens	86-89
34569486-20	2022	CONCLUSION: Ibrutinib is safe and effective in persons with advanced CLL/SLL and better than rituximab in all therapy outcomes including risk of HBV reactivation.	ibrutinib	12-21	solute carrier family 35 member B2	Homo sapiens	73-76
34615723-3	2022	PATIENTS AND METHODS: We conducted a single-center phase I/Ib trial combining a BTK inhibitor (ibrutinib) and a pan-PI3K inhibitor (buparlisib) in 37 patients with relapsed/refractory (R/R) B-cell lymphoma.	ibrutinib	95-104	Bruton tyrosine kinase	Homo sapiens	80-83
34732527-0	2022	Ibrutinib blocks YAP1 activation and reverses BRAFi resistance in melanoma cells.	ibrutinib	0-9	Yes1 associated transcriptional regulator	Homo sapiens	17-21
34732527-4	2022	Ibrutinib is used clinically as a BTK inhibitor; however, neither BTK deletion nor treatment with acalabrutinib, another BTK inhibitor with reduced off-target activity, re-sensitized cells to vemurafenib.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	34-37
34725904-2	2022	Ibrutinib is a first-in-class covalent inhibitor of the Bruton s tyrosine kinase inhibitor that has been approved for the treatment of patients with chronic lymphocytic leukemia, mantle cell lymphoma and Waldenstrom"s macroglobulinemia and is connected with toxicities, caused by high dosage.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	56-80
34791836-12	2022	While nonresponder-associated genes included well-known TP53 and CARD11, genetic classifiers developed using nonresponder-associated genes included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting resistance to ibrutinib may be related to broad biological functions connected to epigenetic modification, telomere maintenance, and cancer-associated signaling pathways (mTOR, JAK/STAT, NF-kappaB).	ibrutinib	217-226	tumor protein p53	Homo sapiens	56-60
34791836-12	2022	While nonresponder-associated genes included well-known TP53 and CARD11, genetic classifiers developed using nonresponder-associated genes included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting resistance to ibrutinib may be related to broad biological functions connected to epigenetic modification, telomere maintenance, and cancer-associated signaling pathways (mTOR, JAK/STAT, NF-kappaB).	ibrutinib	217-226	caspase recruitment domain family member 11	Homo sapiens	65-71
34791836-12	2022	While nonresponder-associated genes included well-known TP53 and CARD11, genetic classifiers developed using nonresponder-associated genes included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting resistance to ibrutinib may be related to broad biological functions connected to epigenetic modification, telomere maintenance, and cancer-associated signaling pathways (mTOR, JAK/STAT, NF-kappaB).	ibrutinib	217-226	ATPase H+ transporting accessory protein 1	Homo sapiens	148-155
34791836-12	2022	While nonresponder-associated genes included well-known TP53 and CARD11, genetic classifiers developed using nonresponder-associated genes included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting resistance to ibrutinib may be related to broad biological functions connected to epigenetic modification, telomere maintenance, and cancer-associated signaling pathways (mTOR, JAK/STAT, NF-kappaB).	ibrutinib	217-226	E1A binding protein p400	Homo sapiens	157-162
34791836-12	2022	While nonresponder-associated genes included well-known TP53 and CARD11, genetic classifiers developed using nonresponder-associated genes included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting resistance to ibrutinib may be related to broad biological functions connected to epigenetic modification, telomere maintenance, and cancer-associated signaling pathways (mTOR, JAK/STAT, NF-kappaB).	ibrutinib	217-226	AT-rich interaction domain 1A	Homo sapiens	164-170
34791836-12	2022	While nonresponder-associated genes included well-known TP53 and CARD11, genetic classifiers developed using nonresponder-associated genes included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting resistance to ibrutinib may be related to broad biological functions connected to epigenetic modification, telomere maintenance, and cancer-associated signaling pathways (mTOR, JAK/STAT, NF-kappaB).	ibrutinib	217-226	suppressor of cytokine signaling 1	Homo sapiens	172-177
34791836-12	2022	While nonresponder-associated genes included well-known TP53 and CARD11, genetic classifiers developed using nonresponder-associated genes included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting resistance to ibrutinib may be related to broad biological functions connected to epigenetic modification, telomere maintenance, and cancer-associated signaling pathways (mTOR, JAK/STAT, NF-kappaB).	ibrutinib	217-226	TBL1X/Y related 1	Homo sapiens	183-190
34791836-12	2022	While nonresponder-associated genes included well-known TP53 and CARD11, genetic classifiers developed using nonresponder-associated genes included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting resistance to ibrutinib may be related to broad biological functions connected to epigenetic modification, telomere maintenance, and cancer-associated signaling pathways (mTOR, JAK/STAT, NF-kappaB).	ibrutinib	217-226	mechanistic target of rapamycin kinase	Homo sapiens	374-378
34791836-12	2022	While nonresponder-associated genes included well-known TP53 and CARD11, genetic classifiers developed using nonresponder-associated genes included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting resistance to ibrutinib may be related to broad biological functions connected to epigenetic modification, telomere maintenance, and cancer-associated signaling pathways (mTOR, JAK/STAT, NF-kappaB).	ibrutinib	217-226	nuclear factor kappa B subunit 1	Homo sapiens	390-399
34732527-5	2022	These data suggest that ibrutinib acts through a BTK-independent mechanism in vemurafenib re-sensitization.	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	49-52
34732527-8	2022	Furthermore, genes that are differentially expressed in ibrutinib-treated cells are enriched in YAP1 target genes and we showed that ibrutinib, but not acalabrutinib, reduces YAP1 activity in BRAFi-resistant melanoma cells.	ibrutinib	56-65	Yes1 associated transcriptional regulator	Homo sapiens	175-179
34732527-8	2022	Furthermore, genes that are differentially expressed in ibrutinib-treated cells are enriched in YAP1 target genes and we showed that ibrutinib, but not acalabrutinib, reduces YAP1 activity in BRAFi-resistant melanoma cells.	ibrutinib	133-142	Yes1 associated transcriptional regulator	Homo sapiens	175-179
34521099-0	2021	Ibrutinib induces durable remissions in treatment-naive patients with CLL and 17p deletion/TP53 mutations.	ibrutinib	0-9	tumor protein p53	Homo sapiens	91-95
34954235-0	2022	The conformational state of the BTK substrate PLCgamma contributes to Ibrutinib resistance.	ibrutinib	70-79	Bruton tyrosine kinase	Homo sapiens	32-35
34954235-1	2022	Mutations in PLCgamma, a substrate of the tyrosine kinase BTK, are often found in patients who develop resistance to the BTK inhibitor Ibrutinib.	ibrutinib	135-144	Bruton tyrosine kinase	Homo sapiens	58-61
34954235-1	2022	Mutations in PLCgamma, a substrate of the tyrosine kinase BTK, are often found in patients who develop resistance to the BTK inhibitor Ibrutinib.	ibrutinib	135-144	Bruton tyrosine kinase	Homo sapiens	121-124
34959482-6	2021	The irreversible BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, and spebrutinib) covalently bind to the C481 amino acid of BTK.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	17-20
34959482-6	2021	The irreversible BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, and spebrutinib) covalently bind to the C481 amino acid of BTK.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	146-149
34890967-6	2022	Inhibition of BTK by ibrutinib not only suppressed the migration and invasion-promoting ability, but also declined the increased expression of p-BTK, p-Akt, beta-catenin, and CSC markers upon REC8 overexpression.	ibrutinib	21-30	Bruton tyrosine kinase	Homo sapiens	14-17
34890967-6	2022	Inhibition of BTK by ibrutinib not only suppressed the migration and invasion-promoting ability, but also declined the increased expression of p-BTK, p-Akt, beta-catenin, and CSC markers upon REC8 overexpression.	ibrutinib	21-30	Bruton tyrosine kinase	Homo sapiens	145-148
34890967-6	2022	Inhibition of BTK by ibrutinib not only suppressed the migration and invasion-promoting ability, but also declined the increased expression of p-BTK, p-Akt, beta-catenin, and CSC markers upon REC8 overexpression.	ibrutinib	21-30	AKT serine/threonine kinase 1	Homo sapiens	152-155
34890967-6	2022	Inhibition of BTK by ibrutinib not only suppressed the migration and invasion-promoting ability, but also declined the increased expression of p-BTK, p-Akt, beta-catenin, and CSC markers upon REC8 overexpression.	ibrutinib	21-30	catenin beta 1	Homo sapiens	157-169
34890967-6	2022	Inhibition of BTK by ibrutinib not only suppressed the migration and invasion-promoting ability, but also declined the increased expression of p-BTK, p-Akt, beta-catenin, and CSC markers upon REC8 overexpression.	ibrutinib	21-30	REC8 meiotic recombination protein	Homo sapiens	192-196
34965304-14	2022	Our study confirms the predictive and prognostic value of CXCR4 mutations in patients with WM treated with ibrutinib monotherapy.	ibrutinib	107-116	C-X-C motif chemokine receptor 4	Homo sapiens	58-63
34970462-5	2021	Here, we describe a case of a 76-year-old Caucasian male patient who moved from California to Wisconsin with a history of coccidioidomycosis infection of the left knee that reactivated decades later in his prosthetic knee shortly after being initiated on ibrutinib (Imbruvica), a Bruton tyrosine kinase (BTK) inhibitor, for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).	ibrutinib	255-264	Bruton tyrosine kinase	Homo sapiens	280-302
34970462-5	2021	Here, we describe a case of a 76-year-old Caucasian male patient who moved from California to Wisconsin with a history of coccidioidomycosis infection of the left knee that reactivated decades later in his prosthetic knee shortly after being initiated on ibrutinib (Imbruvica), a Bruton tyrosine kinase (BTK) inhibitor, for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).	ibrutinib	255-264	Bruton tyrosine kinase	Homo sapiens	304-307
34521099-1	2021	Ibrutinib, the first-in class Bruton"s tyrosine kinase (BTK) inhibitor, has become a preferred treatment for patients with CLL, based on improved progression free and overall survival (PFS, OS) when compared to previous standard chemo-(+/-) immunotherapy regimen, in the frontline and relapsed disease settings.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	30-54
34521099-1	2021	Ibrutinib, the first-in class Bruton"s tyrosine kinase (BTK) inhibitor, has become a preferred treatment for patients with CLL, based on improved progression free and overall survival (PFS, OS) when compared to previous standard chemo-(+/-) immunotherapy regimen, in the frontline and relapsed disease settings.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	56-59
34521099-3	2021	Here, we report the long-term outcome of 27 patients with CLL treatment naive with 17p deletion and/or TP53 mutation treated with ibrutinib alone or in combination with rituximab on a Phase-2 clinical study.	ibrutinib	130-139	tumor protein p53	Homo sapiens	103-107
34521099-5	2021	These data corroborate that ibrutinib therapy, induces durable remissions in patients with 17p deletion and/or TP53 mutations, and suggest that BTK inhibitor therapy should be a preferred treatment for these patients outside of clinical trials.	ibrutinib	28-37	tumor protein p53	Homo sapiens	111-115
34895246-7	2021	To pharmacologically inhibit BTK, a specific inhibitor ibrutinib was used.	ibrutinib	55-64	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	29-32
34897650-5	2022	Moreover, we demonstrated that pharmacological inhibition of BTK with ibrutinib specifically inhibits neutrophil and Ly6Chi monocytes, but not Ly6Clo monocyte recruitment to the peritoneum.	ibrutinib	70-79	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	61-64
34739844-4	2021	The 3-year event-free survival of younger patients (age <=60 years) treated with ibrutinib plus R-CHOP was 100% in the MCD and N1 subtypes while the survival of patients with these subtypes treated with R-CHOP alone was significantly inferior (42.9% and 50%, respectively).	ibrutinib	81-90	DNA damage inducible transcript 3	Homo sapiens	205-209
34895246-16	2021	Next, we conducted proof-of-concept pharmacological BTK inhibitor studies with ibrutinib and LFM-A13.	ibrutinib	79-88	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	52-55
34865212-0	2022	Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials.	ibrutinib	33-42	tumor protein p53	Homo sapiens	104-108
34280258-3	2021	Both genetic inactivation of Bruton"s Tyrosine Kinase (BTK) and pharmacological inhibition by the BTK inhibitor ibrutinib strongly synergize with ASNase by inhibiting the amino acid response pathway, a mechanism involving c-Myc mediated suppression of GCN2 activity.	ibrutinib	112-121	Bruton tyrosine kinase	Homo sapiens	98-101
34280258-3	2021	Both genetic inactivation of Bruton"s Tyrosine Kinase (BTK) and pharmacological inhibition by the BTK inhibitor ibrutinib strongly synergize with ASNase by inhibiting the amino acid response pathway, a mechanism involving c-Myc mediated suppression of GCN2 activity.	ibrutinib	112-121	eukaryotic translation initiation factor 2 alpha kinase 4	Homo sapiens	252-256
34865212-3	2022	The pooled analysis included 89 patients with TP53 aberrations receiving first-line treatment with single-agent ibrutinib (n = 45) or ibrutinib in combination with an anti-CD20 antibody (n = 44).	ibrutinib	112-121	tumor protein p53	Homo sapiens	46-50
34605340-0	2021	Ibrutinib ameliorates cerebral ischemia/reperfusion injury through autophagy activation and PI3K/Akt/mTOR signaling pathway in diabetic mice.	ibrutinib	0-9	thymoma viral proto-oncogene 1	Mus musculus	97-100
34632931-1	2021	Ibrutinib (Imbruvica , 2013) is a Bruton"s tyrosine kinase (BTK) inhibitor approved for multiple B-cell malignancies and cGVHD.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	34-58
34632931-1	2021	Ibrutinib (Imbruvica , 2013) is a Bruton"s tyrosine kinase (BTK) inhibitor approved for multiple B-cell malignancies and cGVHD.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	60-63
34632931-5	2021	identified that ibrutinib-mediated atrial fibrillation is likely due to off-target CSK inhibition.	ibrutinib	16-25	C-terminal Src kinase	Homo sapiens	83-86
34625994-10	2021	When treatment is indicated, several therapeutic options exist: a combination of the BCL2 inhibitor venetoclax with obinutuzumab, monotherapy with inhibitors of Bruton tyrosine kinase (BTK) such as ibrutinib and acalabrutinib, or chemoimmunotherapy.	ibrutinib	198-207	Bruton tyrosine kinase	Homo sapiens	161-183
34605340-0	2021	Ibrutinib ameliorates cerebral ischemia/reperfusion injury through autophagy activation and PI3K/Akt/mTOR signaling pathway in diabetic mice.	ibrutinib	0-9	mechanistic target of rapamycin kinase	Mus musculus	101-105
34605340-3	2021	We aim to investigate the regulatory role and potential mechanism of ibrutinib, a selective inhibitor of BTK, in cerebral I/R injured diabetic mice.	ibrutinib	69-78	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	105-108
34605340-10	2021	Furthermore, the expression of PI3K/AKT/mTOR pathway-related proteins were significantly upregulated by ibrutinib treatment.	ibrutinib	104-113	thymoma viral proto-oncogene 1	Mus musculus	36-39
34605340-10	2021	Furthermore, the expression of PI3K/AKT/mTOR pathway-related proteins were significantly upregulated by ibrutinib treatment.	ibrutinib	104-113	mechanistic target of rapamycin kinase	Mus musculus	40-44
34605340-11	2021	In summary, our finding collectively demonstrated that Ibrutinib could effectively ameliorate cerebral ischemia/reperfusion injury via ameliorating inflammatory response, oxidative stress, and improving autophagy through PI3K/Akt/mTOR signaling pathway in diabetic mice.	ibrutinib	55-64	thymoma viral proto-oncogene 1	Mus musculus	226-229
34605340-11	2021	In summary, our finding collectively demonstrated that Ibrutinib could effectively ameliorate cerebral ischemia/reperfusion injury via ameliorating inflammatory response, oxidative stress, and improving autophagy through PI3K/Akt/mTOR signaling pathway in diabetic mice.	ibrutinib	55-64	mechanistic target of rapamycin kinase	Mus musculus	230-234
34534359-5	2021	To extort this role, BTK inhibitors such as Ibrutinib have been developed to target BTK in other diseases.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	21-24
34605364-1	2021	OBJECTIVES: Ibrutinib, a potent inhibitor of the Bruton tyrosine kinase, has revolutionized the treatment of many B-cell malignancies.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	49-71
34534359-5	2021	To extort this role, BTK inhibitors such as Ibrutinib have been developed to target BTK in other diseases.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	84-87
34912339-1	2021	Bacterial infections are a major cause of morbidity and mortality in chronic lymphocytic leukemia (CLL), and infection risk increases in patients treated with the Bruton"s tyrosine kinase (Btk) inhibitor, ibrutinib.	ibrutinib	205-214	Bruton tyrosine kinase	Homo sapiens	163-187
33567947-1	2021	The introduction of Bruton"s tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies.	ibrutinib	55-64	Bruton tyrosine kinase	Homo sapiens	20-44
34481113-3	2021	Ibrutinib is a Bruton Tyrosine Kinase and Interleukin-2 Inducible Kinase inhibitor thought to affect pathways driving cGVHD, and it was approved for the treatment of refractory cGVHD by the Food and Drug Administration in August 2017 after a landmark Phase 1b/2 study.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	15-37
34912339-1	2021	Bacterial infections are a major cause of morbidity and mortality in chronic lymphocytic leukemia (CLL), and infection risk increases in patients treated with the Bruton"s tyrosine kinase (Btk) inhibitor, ibrutinib.	ibrutinib	205-214	Bruton tyrosine kinase	Homo sapiens	189-192
34912339-2	2021	Btk and related kinases (like Tec) are expressed in non-leukemic hematopoietic cells and can be targeted by ibrutinib.	ibrutinib	108-117	Bruton tyrosine kinase	Homo sapiens	0-3
34912339-2	2021	Btk and related kinases (like Tec) are expressed in non-leukemic hematopoietic cells and can be targeted by ibrutinib.	ibrutinib	108-117	tec protein tyrosine kinase	Homo sapiens	30-33
34912339-10	2021	In respect of intracellular signaling, bacteria induced Btk and Tec phosphorylation in both CLL and control platelets that was inhibited by ibrutinib.	ibrutinib	140-149	Bruton tyrosine kinase	Homo sapiens	56-59
34912339-10	2021	In respect of intracellular signaling, bacteria induced Btk and Tec phosphorylation in both CLL and control platelets that was inhibited by ibrutinib.	ibrutinib	140-149	tec protein tyrosine kinase	Homo sapiens	64-67
34912339-12	2021	Our data suggest that ibrutinib impairment of FcgammaRIIA-mediated platelet activation by bacteria results from a combination of Btk and Tec inhibition, although off-target effects on additional kinases cannot be discarded.	ibrutinib	22-31	Bruton tyrosine kinase	Homo sapiens	129-132
34912339-12	2021	Our data suggest that ibrutinib impairment of FcgammaRIIA-mediated platelet activation by bacteria results from a combination of Btk and Tec inhibition, although off-target effects on additional kinases cannot be discarded.	ibrutinib	22-31	tec protein tyrosine kinase	Homo sapiens	137-140
34809665-3	2021	METHODS: In this study, we examined both the in vitro effect and long-term in vivo effect of two clinically available BTKi, ibrutinib and zanubrutinib.	ibrutinib	124-133	inhibitor of Bruton tyrosine kinase	Homo sapiens	118-122
34884478-2	2021	Herein, we comparatively evaluated the single and combined application of the BTK inhibitor ibrutinib and the selective PI3Kgamma inhibitor AS-605240 in the canine DLBCL cell line CLBL-1.	ibrutinib	92-101	Bruton tyrosine kinase	Canis lupus familiaris	78-81
34884478-6	2021	Moreover, the combined application of ibrutinib and AS-605240 reduced relative phosphorylation and, in some instances, the levels of the BTK, AKT, GSK3beta, and ERK proteins.	ibrutinib	38-47	Bruton tyrosine kinase	Homo sapiens	137-140
34884478-6	2021	Moreover, the combined application of ibrutinib and AS-605240 reduced relative phosphorylation and, in some instances, the levels of the BTK, AKT, GSK3beta, and ERK proteins.	ibrutinib	38-47	glycogen synthase kinase 3 alpha	Canis lupus familiaris	147-155
34795418-5	2022	Combinatorial treatment further efficiently overcomes both primary and acquired resistance to venetoclax, which we could link to reduced expression of the Bcl-2 family members Bcl-XL and Bcl-2A1 under ibrutinib.	ibrutinib	201-210	BCL2 like 1	Homo sapiens	176-182
34858727-6	2021	The BTK inhibitor ibrutinib effectively blocked tumor cell-intrinsic IL-10 expression and tumor growth in this Myc-driven model.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
34858727-6	2021	The BTK inhibitor ibrutinib effectively blocked tumor cell-intrinsic IL-10 expression and tumor growth in this Myc-driven model.	ibrutinib	18-27	interleukin 10	Homo sapiens	69-74
34858727-6	2021	The BTK inhibitor ibrutinib effectively blocked tumor cell-intrinsic IL-10 expression and tumor growth in this Myc-driven model.	ibrutinib	18-27	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	111-114
34798905-1	2021	BACKGROUND: Ibrutinib is a Bruton"s tyrosine kinase inhibitor used in the treatment of hematological malignancies.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	27-51
34132782-0	2021	The HCK/BTK inhibitor KIN-8194 is active in MYD88 driven lymphomas and overcomes mutated BTKCys481 ibrutinib resistance.	ibrutinib	99-108	hemopoietic cell kinase	Mus musculus	4-7
34132782-0	2021	The HCK/BTK inhibitor KIN-8194 is active in MYD88 driven lymphomas and overcomes mutated BTKCys481 ibrutinib resistance.	ibrutinib	99-108	Kin17 DNA and RNA binding protein	Mus musculus	22-25
34132782-2	2021	Ibrutinib binds to BTKCys481 and is active in B-cell malignancies driven by mutated MYD88.	ibrutinib	0-9	myeloid differentiation primary response gene 88	Mus musculus	84-89
34132782-5	2021	KIN-8194 showed potent and selective in vitro killing of MYD88 mutated lymphoma cells, including ibrutinib resistant BTKCys481Ser expressing cells.	ibrutinib	97-106	Kin17 DNA and RNA binding protein	Homo sapiens	0-3
34795418-2	2022	Here, we use single and combinatorial drug response profiling to show that the combined inhibition of the anti-apoptotic protein Bcl-2 and of the tyrosine kinase BTK with the small molecules venetoclax and ibrutinib efficiently kills DLBCL cells in vitro.	ibrutinib	206-215	BCL2 apoptosis regulator	Homo sapiens	129-134
34795418-2	2022	Here, we use single and combinatorial drug response profiling to show that the combined inhibition of the anti-apoptotic protein Bcl-2 and of the tyrosine kinase BTK with the small molecules venetoclax and ibrutinib efficiently kills DLBCL cells in vitro.	ibrutinib	206-215	Bruton tyrosine kinase	Homo sapiens	162-165
34782617-8	2021	We further confirmed that NUSAP1 reduction enhanced the sensitivity of CLL cells to fludarabine or ibrutinib.	ibrutinib	99-108	nucleolar and spindle associated protein 1	Homo sapiens	26-32
34795418-5	2022	Combinatorial treatment further efficiently overcomes both primary and acquired resistance to venetoclax, which we could link to reduced expression of the Bcl-2 family members Bcl-XL and Bcl-2A1 under ibrutinib.	ibrutinib	201-210	BCL2 apoptosis regulator	Homo sapiens	155-160
34795418-5	2022	Combinatorial treatment further efficiently overcomes both primary and acquired resistance to venetoclax, which we could link to reduced expression of the Bcl-2 family members Bcl-XL and Bcl-2A1 under ibrutinib.	ibrutinib	201-210	BCL2 related protein A1	Homo sapiens	187-194
34795418-6	2022	We found in a Swiss DLBCL cohort that ~15% of patients are projected to respond to the venetoclax/ibrutinib combination based on their high Bcl-2 expression and nuclear NF-kappaB localization.	ibrutinib	98-107	BCL2 apoptosis regulator	Homo sapiens	140-145
34726066-1	2021	Background Ibrutinib and acalabrutinib are Bruton tyrosine kinase inhibitors used in the treatment of B-cell lymphoproliferative disorders.	ibrutinib	11-20	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	43-65
34672559-2	2021	However, there is an urgent need to discover more selective covalent BTK inhibitors owing to the off-target adverse effects of the approved inhibitor, ibrutinib.	ibrutinib	151-160	Bruton tyrosine kinase	Homo sapiens	69-72
34750354-2	2021	Ibrutinib is a first-in class, oral, covalent Bruton"s tyrosine kinase (BTK) inhibitor (BTKi) that has shown impressive clinical activity, yet many ibrutinib-treated patients relapse or develop resistance over time.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	46-70
34858810-2	2021	Ibrutinib, the first-in-class BTK inhibitor, is approved by the US FDA to treat patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL; after >=1 prior therapy); and by the European Medicines Agency (EMA) for adult patients with relapsed/refractory (R/R) MCL and patients with CLL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	30-33
34750354-2	2021	Ibrutinib is a first-in class, oral, covalent Bruton"s tyrosine kinase (BTK) inhibitor (BTKi) that has shown impressive clinical activity, yet many ibrutinib-treated patients relapse or develop resistance over time.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	72-75
34750354-2	2021	Ibrutinib is a first-in class, oral, covalent Bruton"s tyrosine kinase (BTK) inhibitor (BTKi) that has shown impressive clinical activity, yet many ibrutinib-treated patients relapse or develop resistance over time.	ibrutinib	0-9	inhibitor of Bruton tyrosine kinase	Homo sapiens	88-92
34750354-3	2021	We have reported that acquired resistance to ibrutinib is associated with downregulation of tumor suppressor protein PTEN and activation of the PI3K/AKT pathway.	ibrutinib	45-54	phosphatase and tensin homolog	Homo sapiens	117-121
34750354-3	2021	We have reported that acquired resistance to ibrutinib is associated with downregulation of tumor suppressor protein PTEN and activation of the PI3K/AKT pathway.	ibrutinib	45-54	AKT serine/threonine kinase 1	Homo sapiens	149-152
34750354-5	2021	We now show that the BTKi ibrutinib and a second-generation compound, acalabrutinib downregulate miRNAs located in the 14q32 miRNA cluster region, including miR-494, miR-495, and miR-543.	ibrutinib	26-35	inhibitor of Bruton tyrosine kinase	Homo sapiens	21-25
34750354-5	2021	We now show that the BTKi ibrutinib and a second-generation compound, acalabrutinib downregulate miRNAs located in the 14q32 miRNA cluster region, including miR-494, miR-495, and miR-543.	ibrutinib	26-35	microRNA 494	Homo sapiens	157-164
34750354-5	2021	We now show that the BTKi ibrutinib and a second-generation compound, acalabrutinib downregulate miRNAs located in the 14q32 miRNA cluster region, including miR-494, miR-495, and miR-543.	ibrutinib	26-35	microRNA 495	Homo sapiens	166-173
34750354-5	2021	We now show that the BTKi ibrutinib and a second-generation compound, acalabrutinib downregulate miRNAs located in the 14q32 miRNA cluster region, including miR-494, miR-495, and miR-543.	ibrutinib	26-35	microRNA 543	Homo sapiens	179-186
34750354-7	2021	Additionally, unlike ibrutinib-sensitive CLL patient samples, those with resistance to ibrutinib treatment, demonstrated upregulation of 14q32 cluster miRNAs, including miR-494, miR-495, and miR-543 and decreased pten mRNA expression.	ibrutinib	21-30	microRNA 494	Homo sapiens	169-176
34750354-7	2021	Additionally, unlike ibrutinib-sensitive CLL patient samples, those with resistance to ibrutinib treatment, demonstrated upregulation of 14q32 cluster miRNAs, including miR-494, miR-495, and miR-543 and decreased pten mRNA expression.	ibrutinib	21-30	microRNA 495	Homo sapiens	178-185
34750354-7	2021	Additionally, unlike ibrutinib-sensitive CLL patient samples, those with resistance to ibrutinib treatment, demonstrated upregulation of 14q32 cluster miRNAs, including miR-494, miR-495, and miR-543 and decreased pten mRNA expression.	ibrutinib	21-30	microRNA 543	Homo sapiens	191-198
34750354-7	2021	Additionally, unlike ibrutinib-sensitive CLL patient samples, those with resistance to ibrutinib treatment, demonstrated upregulation of 14q32 cluster miRNAs, including miR-494, miR-495, and miR-543 and decreased pten mRNA expression.	ibrutinib	21-30	phosphatase and tensin homolog	Homo sapiens	213-217
34750354-7	2021	Additionally, unlike ibrutinib-sensitive CLL patient samples, those with resistance to ibrutinib treatment, demonstrated upregulation of 14q32 cluster miRNAs, including miR-494, miR-495, and miR-543 and decreased pten mRNA expression.	ibrutinib	87-96	microRNA 494	Homo sapiens	169-176
34750354-7	2021	Additionally, unlike ibrutinib-sensitive CLL patient samples, those with resistance to ibrutinib treatment, demonstrated upregulation of 14q32 cluster miRNAs, including miR-494, miR-495, and miR-543 and decreased pten mRNA expression.	ibrutinib	87-96	microRNA 495	Homo sapiens	178-185
34750354-7	2021	Additionally, unlike ibrutinib-sensitive CLL patient samples, those with resistance to ibrutinib treatment, demonstrated upregulation of 14q32 cluster miRNAs, including miR-494, miR-495, and miR-543 and decreased pten mRNA expression.	ibrutinib	87-96	microRNA 543	Homo sapiens	191-198
34750354-7	2021	Additionally, unlike ibrutinib-sensitive CLL patient samples, those with resistance to ibrutinib treatment, demonstrated upregulation of 14q32 cluster miRNAs, including miR-494, miR-495, and miR-543 and decreased pten mRNA expression.	ibrutinib	87-96	phosphatase and tensin homolog	Homo sapiens	213-217
34334330-1	2021	INTRODUCTION: The Alliance A041202/CCTG CLC.2 trial demonstrated superior progression-free survival with ibrutinib-based therapy compared to chemoimmunotherapy with bendamustine-rituximab (BR) in previously untreated older patients with chronic lymphocytic leukemia.	ibrutinib	105-114	chaperonin containing TCP1 subunit 3	Homo sapiens	35-39
34732719-4	2021	Indeed, here we report overexpression of human MTCP1 restricted to the B cell compartment in mice produces a clonal CD5+/CD19+ leukemia recapitulating the major characteristics of human CLL and demonstrates favorable response to therapeutic intervention with ibrutinib.	ibrutinib	259-268	mature T cell proliferation 1	Homo sapiens	47-52
34726785-1	2022	Ibrutinib is a Bruton tyrosine kinase inhibitor used to treat many hematologic conditions, most commonly B-cell lymphomas and leukemias.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	15-37
34274291-5	2021	In patients with un-mutated (but not with mutated) IGHV higher PFS proportions and favorable HRs were observed for acalabrutinib, acalabrutinib-plus-obinutuzumab, and ibrutinib-plus-obinutuzumab relative to ibrutinib; and targeted therapies were superior over chemoimmunotherapies in patients with del 17p.	ibrutinib	167-176	immunoglobulin heavy variable 3-69-1 (pseudogene)	Homo sapiens	51-55
34274291-5	2021	In patients with un-mutated (but not with mutated) IGHV higher PFS proportions and favorable HRs were observed for acalabrutinib, acalabrutinib-plus-obinutuzumab, and ibrutinib-plus-obinutuzumab relative to ibrutinib; and targeted therapies were superior over chemoimmunotherapies in patients with del 17p.	ibrutinib	207-216	immunoglobulin heavy variable 3-69-1 (pseudogene)	Homo sapiens	51-55
34474146-0	2021	miRNA-223-3p modulates ibrutinib resistance through regulating CHUK/NF-kappaB signaling pathway in mantle cell lymphoma.	ibrutinib	23-32	component of inhibitor of nuclear factor kappa B kinase complex	Homo sapiens	63-67
34474146-0	2021	miRNA-223-3p modulates ibrutinib resistance through regulating CHUK/NF-kappaB signaling pathway in mantle cell lymphoma.	ibrutinib	23-32	nuclear factor kappa B subunit 1	Homo sapiens	68-77
34474146-1	2021	With the application of Brutons tyrosine kinase(BTK) inhibitor ibrutinib in relapsed / refractory (R/R) mantle cell lymphoma (MCL), the problem of drug resistance is increasingly prominent.	ibrutinib	63-72	Bruton tyrosine kinase	Homo sapiens	24-47
34474146-1	2021	With the application of Brutons tyrosine kinase(BTK) inhibitor ibrutinib in relapsed / refractory (R/R) mantle cell lymphoma (MCL), the problem of drug resistance is increasingly prominent.	ibrutinib	63-72	Bruton tyrosine kinase	Homo sapiens	48-51
34950932-0	2021	Intentional Modulation of Ibrutinib Pharmacokinetics through CYP3A Inhibition.	ibrutinib	26-35	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	61-66
34474146-2	2021	Though non-classical nuclear factor kappa-B pathway (non-classical NF-kappaB pathway) has been proved to be correlated with ibrutinib resistance in MCL, the upstream regulator is unknown.	ibrutinib	124-133	nuclear factor kappa B subunit 1	Homo sapiens	67-76
34950932-3	2021	We hypothesized that the oral bioavailability of ibrutinib is limited by CYP3A isoform-mediated metabolism, and that this pathway can be inhibited to improve the pharmacokinetic properties of ibrutinib.	ibrutinib	49-58	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	73-78
34474146-3	2021	In the present study, CHUK overexpression accelerated proliferation and suppressed apoptosis of MCL cells after ibrutinib treatment in vitro.	ibrutinib	112-121	component of inhibitor of nuclear factor kappa B kinase complex	Homo sapiens	22-26
34950932-5	2021	Computational modeling was performed to derive doses of ibrutinib that, when given after a CYP3A inhibitor, results in therapeutically-relevant drug levels.	ibrutinib	56-65	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	91-96
34950932-6	2021	Deficiency of CYP3A in mice was associated with a ~10-fold increase in the area under the curve of ibrutinib.	ibrutinib	99-108	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	14-19
34474146-6	2021	In conclusion, miRNA-223-3p modulates ibrutinib resistance through regulating CHUK/NF-kappaB signaling pathway in MCL, which is crucial to provide a marker to predict disease response.	ibrutinib	38-47	component of inhibitor of nuclear factor kappa B kinase complex	Homo sapiens	78-82
34950932-9	2021	These findings signify a dominant role for CYP3A-mediated metabolism in the elimination of ibrutinib, and suggest a role for pharmacological inhibitors of this pathway to intentionally modulate the plasma levels and improve the therapeutic use of this clinically important agent.	ibrutinib	91-100	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	43-48
34474146-6	2021	In conclusion, miRNA-223-3p modulates ibrutinib resistance through regulating CHUK/NF-kappaB signaling pathway in MCL, which is crucial to provide a marker to predict disease response.	ibrutinib	38-47	nuclear factor kappa B subunit 1	Homo sapiens	83-92
34310172-1	2021	PURPOSE: Among Bruton"s tyrosine kinase inhibitors, acalabrutinib has greater selectivity than ibrutinib, which we hypothesized would improve continuous therapy tolerability.	ibrutinib	95-104	Bruton tyrosine kinase	Homo sapiens	15-39
34289017-3	2021	We conducted a Phase I trial of the CXCR4-antagonist ulocuplumab with ibrutinib in this first-ever study to target CXCR4Mut in WM.	ibrutinib	70-79	C-X-C motif chemokine receptor 4	Homo sapiens	115-123
34771616-0	2021	Targeting of HSP70/HSF1 Axis Abrogates In Vitro Ibrutinib-Resistance in Chronic Lymphocytic Leukemia.	ibrutinib	48-57	heat shock protein family A (Hsp70) member 4	Homo sapiens	13-18
34771616-0	2021	Targeting of HSP70/HSF1 Axis Abrogates In Vitro Ibrutinib-Resistance in Chronic Lymphocytic Leukemia.	ibrutinib	48-57	heat shock transcription factor 1	Homo sapiens	19-23
34771616-1	2021	The Btk inhibitor ibrutinib has significantly changed the management of chronic lymphocytic leukemia (CLL) patients.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
34771616-3	2021	Although BTK and PLCgamma2 mutations have been found to be associated with ibrutinib resistance in a fair percentage of CLL patients, no information on resistance mechanisms is available in patients lacking these mutations.	ibrutinib	75-84	Bruton tyrosine kinase	Homo sapiens	9-12
34771616-3	2021	Although BTK and PLCgamma2 mutations have been found to be associated with ibrutinib resistance in a fair percentage of CLL patients, no information on resistance mechanisms is available in patients lacking these mutations.	ibrutinib	75-84	phospholipase C gamma 2	Homo sapiens	17-26
34771616-8	2021	We suggest an involvement of HSP70/HSF1 axis in controlling resistance to ibrutinib in CLL cells, since their inhibition is effective in inducing in vitro apoptosis in cells from ibrutinib refractory patients.	ibrutinib	74-83	heat shock protein family A (Hsp70) member 4	Homo sapiens	29-34
34771616-8	2021	We suggest an involvement of HSP70/HSF1 axis in controlling resistance to ibrutinib in CLL cells, since their inhibition is effective in inducing in vitro apoptosis in cells from ibrutinib refractory patients.	ibrutinib	74-83	heat shock transcription factor 1	Homo sapiens	35-39
34744463-3	2021	The first-generation inhibitor, ibrutinib, covalently binds to the C481 amino acid of Bruton"s tyrosine kinase (BTK), thereby irreversibly inhibiting its kinase activity, and interferes with the biology of the cells, ultimately resulting in CLL cell death and therapeutic response.	ibrutinib	32-41	Bruton tyrosine kinase	Homo sapiens	86-110
34744463-3	2021	The first-generation inhibitor, ibrutinib, covalently binds to the C481 amino acid of Bruton"s tyrosine kinase (BTK), thereby irreversibly inhibiting its kinase activity, and interferes with the biology of the cells, ultimately resulting in CLL cell death and therapeutic response.	ibrutinib	32-41	Bruton tyrosine kinase	Homo sapiens	112-115
34778053-0	2021	Clinical Trials of the BTK Inhibitors Ibrutinib and Acalabrutinib in Human Diseases Beyond B Cell Malignancies.	ibrutinib	38-47	Bruton tyrosine kinase	Homo sapiens	23-26
34778053-1	2021	The BTK inhibitors ibrutinib and acalabrutinib are FDA-approved drugs for the treatment of B cell malignances.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	4-7
34699590-10	2021	Agents such as the Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs (IMiDs) like lenalidomide or pomalidomide have shown promising response rates in the clinical trial setting for recurrent/refractory PCNSL and are increasingly being adopted in clinical use.	ibrutinib	58-67	Bruton tyrosine kinase	Homo sapiens	19-41
34771535-5	2021	Novel treatment strategies such as the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3 kinase (PI3K) inhibitors, and immunomodulatory drugs are promising.	ibrutinib	80-89	Bruton tyrosine kinase	Homo sapiens	39-63
34771535-5	2021	Novel treatment strategies such as the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3 kinase (PI3K) inhibitors, and immunomodulatory drugs are promising.	ibrutinib	80-89	Bruton tyrosine kinase	Homo sapiens	65-68
34699590-10	2021	Agents such as the Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs (IMiDs) like lenalidomide or pomalidomide have shown promising response rates in the clinical trial setting for recurrent/refractory PCNSL and are increasingly being adopted in clinical use.	ibrutinib	58-67	Bruton tyrosine kinase	Homo sapiens	43-46
34662393-1	2022	Covalent Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib have proven to be highly beneficial in the treatment of chronic lymphocytic leukemia (CLL).	ibrutinib	57-66	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	9-31
34315173-5	2021	Furthermore, we found that activation was dependent on FcgammaRIIA and we provide in vitro evidence that this pathogenic platelet activation can be counteracted by therapeutic small molecules R406 (fostamatinib) and ibrutinib that inhibit tyrosine kinases Syk and Btk respectively or by the P2Y12 antagonist cangrelor.	ibrutinib	216-225	spleen associated tyrosine kinase	Homo sapiens	256-259
34315173-5	2021	Furthermore, we found that activation was dependent on FcgammaRIIA and we provide in vitro evidence that this pathogenic platelet activation can be counteracted by therapeutic small molecules R406 (fostamatinib) and ibrutinib that inhibit tyrosine kinases Syk and Btk respectively or by the P2Y12 antagonist cangrelor.	ibrutinib	216-225	Bruton tyrosine kinase	Homo sapiens	264-267
34662393-11	2022	Thus, non-covalent BTK/ITK inhibitors such as vecabrutinib may be efficacious in C481S BTK mutant CLL, while preserving the T-cell immunomodulatory function of ibrutinib.	ibrutinib	160-169	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	19-22
34721911-1	2021	Ibrutinib is a targeted therapy drug that blocks the activity of Bruton"s tyrosine kinase, and it is an approved treatment for several mature B-cell malignancies including chronic lymphocytic leukaemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	65-89
34662393-1	2022	Covalent Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib have proven to be highly beneficial in the treatment of chronic lymphocytic leukemia (CLL).	ibrutinib	57-66	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	33-36
34662393-2	2022	Interestingly, the off-target inhibition of IL-2-inducible T-cell kinase (ITK) by ibrutinib may also play a role in modulating the tumor microenvironment, potentially enhancing the treatment benefit.	ibrutinib	82-91	IL2 inducible T cell kinase	Mus musculus	44-72
34662393-2	2022	Interestingly, the off-target inhibition of IL-2-inducible T-cell kinase (ITK) by ibrutinib may also play a role in modulating the tumor microenvironment, potentially enhancing the treatment benefit.	ibrutinib	82-91	IL2 inducible T cell kinase	Mus musculus	74-77
34609751-0	2022	IL2-inducible T-cell kinase inhibitor ibrutinib reduces symptoms and Th2 differentiation in mouse allergic-rhinitis model.	ibrutinib	38-47	IL2 inducible T cell kinase	Mus musculus	0-27
34609751-3	2022	Ibrutinib is an inhibitor for IL2-inducible T-cell kinase, which can promote Th2 and Th17 immune response.	ibrutinib	0-9	IL2 inducible T cell kinase	Mus musculus	30-57
34609751-4	2022	We sought to investigate the effect of ibrutinib on AR and the underlying mechanisms.	ibrutinib	39-48	ferredoxin reductase	Mus musculus	52-54
34609751-5	2022	We established house dust mite-induced AR mouse model and treated AR mice with ibrutinib.	ibrutinib	79-88	ferredoxin reductase	Mus musculus	66-68
34609751-10	2022	Ibrutinib treatment had no effects on the development of lymphocytes and myeloid cells, but alleviated AR symptoms and decreased Th2 cell population in nasal lymphoid tissue.	ibrutinib	0-9	ferredoxin reductase	Mus musculus	103-105
34609751-13	2022	Our results suggested that ibrutinib could ameliorate AR symptoms through suppression of Th2 differentiation in AR mouse model.	ibrutinib	27-36	ferredoxin reductase	Mus musculus	54-56
34609751-13	2022	Our results suggested that ibrutinib could ameliorate AR symptoms through suppression of Th2 differentiation in AR mouse model.	ibrutinib	27-36	ferredoxin reductase	Mus musculus	112-114
34479103-3	2021	Ibrutinib, the first-generation BTK inhibitor, has made a great contribution to the treatment of B cell malignant tumors, but there are still some problems such as resistance or miss target of site mutation.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	32-35
34911327-7	2021	The detection of MYD88 mutation is important for a correct therapeutic strategy, since a Brutons tyrosine kinase inhibitor, ibrutinib, is most effective in patients with mutated MYD88 and wt CXCR4.	ibrutinib	124-133	MYD88 innate immune signal transduction adaptor	Homo sapiens	17-22
34214199-1	2021	BACKGROUND: Despite the unprecedented success of ibrutinib in lymphoma therapy, the development of ibrutinib resistance due to acquired BTK or PLCgamma2 mutations has become a new clinical problem.	ibrutinib	99-108	Bruton tyrosine kinase	Homo sapiens	136-139
34214199-1	2021	BACKGROUND: Despite the unprecedented success of ibrutinib in lymphoma therapy, the development of ibrutinib resistance due to acquired BTK or PLCgamma2 mutations has become a new clinical problem.	ibrutinib	99-108	phospholipase C gamma 2	Homo sapiens	143-152
34214199-5	2021	RESULTS: We show that MCIR1 is a bona fide ibrutinib-resistant MCL cell line with normal BTK-/PLCgamma2 but ibrutinib-resistant ERK1/2 and AKT1 signaling.	ibrutinib	108-117	mitogen-activated protein kinase 3	Homo sapiens	128-134
34214199-5	2021	RESULTS: We show that MCIR1 is a bona fide ibrutinib-resistant MCL cell line with normal BTK-/PLCgamma2 but ibrutinib-resistant ERK1/2 and AKT1 signaling.	ibrutinib	108-117	AKT serine/threonine kinase 1	Homo sapiens	139-143
34214199-8	2021	CONCLUSIONS: We have established the first patient-derived ibrutinib-resistant MCL cell line MCIR1 that lacks BTK or PLCgamma2 mutations but exhibits a hyperactive non-canonical NFkB pathway.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	110-113
34214199-8	2021	CONCLUSIONS: We have established the first patient-derived ibrutinib-resistant MCL cell line MCIR1 that lacks BTK or PLCgamma2 mutations but exhibits a hyperactive non-canonical NFkB pathway.	ibrutinib	59-68	phospholipase C gamma 2	Homo sapiens	117-126
34911327-7	2021	The detection of MYD88 mutation is important for a correct therapeutic strategy, since a Brutons tyrosine kinase inhibitor, ibrutinib, is most effective in patients with mutated MYD88 and wt CXCR4.	ibrutinib	124-133	MYD88 innate immune signal transduction adaptor	Homo sapiens	178-183
34116165-7	2021	In comparison, these drugs had a similar effect on adherence of JeKo-1 cells as the Bruton tyrosine kinase inhibitor ibrutinib, which has a proven anti-tumour effect.	ibrutinib	117-126	Bruton tyrosine kinase	Homo sapiens	84-106
34587719-1	2021	Cardiovascular (CV) toxicities of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib may limit use of this effective therapy in patients with chronic lymphocytic leukemia (CLL).	ibrutinib	77-86	Bruton tyrosine kinase	Homo sapiens	38-60
34587719-1	2021	Cardiovascular (CV) toxicities of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib may limit use of this effective therapy in patients with chronic lymphocytic leukemia (CLL).	ibrutinib	77-86	Bruton tyrosine kinase	Homo sapiens	62-65
34137347-3	2021	The FDA/EMA approval of Ibrutinib, the first-in-class BTK inhibitor, either as monotherapy or in combination with rituximab, changed the treatment landscape of the disease.	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	54-57
34674984-4	2022	The use of Bruton tyrosine kinase inhibitors such as ibrutinib resulted in promising outcomes.	ibrutinib	53-62	Bruton tyrosine kinase	Homo sapiens	11-33
34720938-3	2021	After 3 relapses and intensive treatment with multiple chemotherapy regimens and whole-brain radiotherapy, she received off-label treatment with the Bruton tyrosine kinase inhibitor ibrutinib, responded well, achieved a complete remission, and is progression-free for now >3 years.	ibrutinib	182-191	Bruton tyrosine kinase	Homo sapiens	149-171
34778802-2	2021	We modeled the development of resistance to the BTK inhibitor ibrutinib in the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma, which relies on chronic active BCR signaling for survival.	ibrutinib	62-71	Bruton tyrosine kinase	Homo sapiens	48-51
34508613-5	2021	BGB-3111 provides better safety than another BTK inhibitor, ibrutinib as ibrutinib inhibits the inducible T-cell kinase (ITK) as an off-target effect but BGB-3111 does not inhibit ITK.	ibrutinib	60-69	Bruton tyrosine kinase	Homo sapiens	45-48
34508613-5	2021	BGB-3111 provides better safety than another BTK inhibitor, ibrutinib as ibrutinib inhibits the inducible T-cell kinase (ITK) as an off-target effect but BGB-3111 does not inhibit ITK.	ibrutinib	60-69	IL2 inducible T cell kinase	Homo sapiens	96-119
34508613-5	2021	BGB-3111 provides better safety than another BTK inhibitor, ibrutinib as ibrutinib inhibits the inducible T-cell kinase (ITK) as an off-target effect but BGB-3111 does not inhibit ITK.	ibrutinib	60-69	IL2 inducible T cell kinase	Homo sapiens	121-124
34508613-5	2021	BGB-3111 provides better safety than another BTK inhibitor, ibrutinib as ibrutinib inhibits the inducible T-cell kinase (ITK) as an off-target effect but BGB-3111 does not inhibit ITK.	ibrutinib	73-82	Bruton tyrosine kinase	Homo sapiens	45-48
34508613-5	2021	BGB-3111 provides better safety than another BTK inhibitor, ibrutinib as ibrutinib inhibits the inducible T-cell kinase (ITK) as an off-target effect but BGB-3111 does not inhibit ITK.	ibrutinib	73-82	IL2 inducible T cell kinase	Homo sapiens	96-119
34508613-5	2021	BGB-3111 provides better safety than another BTK inhibitor, ibrutinib as ibrutinib inhibits the inducible T-cell kinase (ITK) as an off-target effect but BGB-3111 does not inhibit ITK.	ibrutinib	73-82	IL2 inducible T cell kinase	Homo sapiens	121-124
34080039-2	2021	The addition of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib to R-CHOP therapy results in increased toxicity versus R-CHOP alone, including higher incidence of peripheral neuropathy.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	20-42
34080039-2	2021	The addition of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib to R-CHOP therapy results in increased toxicity versus R-CHOP alone, including higher incidence of peripheral neuropathy.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	44-47
34080039-8	2021	Extrapolation of the vincristine mechanistic PBPK model to other P-gp substrates further suggested DDI risk when ibrutinib (area under the concentration-time curve (AUC) ratio: 1.8), but not acalabrutinib (AUC ratio: 0.92), was given orally with venetoclax or digoxin.	ibrutinib	113-122	ATP binding cassette subfamily B member 1	Homo sapiens	65-69
34400587-0	2021	Clinical course of COVID-19 in a patient with refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) under ibrutinib therapy.	ibrutinib	129-138	solute carrier family 35 member B2	Homo sapiens	118-121
34371149-0	2021	HOT-MELT EXTRUSION BASED SUSTAINED RELEASE IBRUTINIB DELIVERY SYSTEM: AN INHIBITOR OF BRUTON"S TYROSINE KINASE (BTK).	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	112-115
34371149-1	2021	Ibrutinib (IB) is the first Bruton"s tyrosine kinase (BTK) inhibitor classified as BCS class-II, with multiple polymorphic forms.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	28-52
34371149-1	2021	Ibrutinib (IB) is the first Bruton"s tyrosine kinase (BTK) inhibitor classified as BCS class-II, with multiple polymorphic forms.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	54-57
34371149-1	2021	Ibrutinib (IB) is the first Bruton"s tyrosine kinase (BTK) inhibitor classified as BCS class-II, with multiple polymorphic forms.	ibrutinib	11-13	Bruton tyrosine kinase	Homo sapiens	28-52
34371149-1	2021	Ibrutinib (IB) is the first Bruton"s tyrosine kinase (BTK) inhibitor classified as BCS class-II, with multiple polymorphic forms.	ibrutinib	11-13	Bruton tyrosine kinase	Homo sapiens	54-57
34558376-5	2021	DATA SUMMARY: The first-generation Bruton tyrosine kinase inhibitor ibrutinib received Food and Drug Administration approval for Waldenstrom macroglobulinemia in 2015; this was the first drug approved for this rare condition.	ibrutinib	68-77	Bruton tyrosine kinase	Homo sapiens	35-57
34275396-1	2021	INTRODUCTION: The first-in-class BTK inhibitor ibrutinib has substantially changed the therapeutic landscape of chronic lymphocytic leukaemia (CLL).	ibrutinib	47-56	Bruton tyrosine kinase	Homo sapiens	33-36
34345815-8	2021	Currently, BTK inhibitors such as ibrutinib and acalabrutinib have shown a protective effect against pulmonary injury in a small series group of COVID-19 infected patients.	ibrutinib	34-43	Bruton tyrosine kinase	Homo sapiens	11-14
34375536-8	2021	A reduced dose of ibrutinib with the concurrent use of CYP3A inhibitors such as antifungal agents could be an attractive strategy to reduce toxicities and may confer financial benefits.	ibrutinib	18-27	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	55-60
34692401-3	2021	Ibrutinib, a Bruton tyrosine kinase inhibitor, has had success in some patients with high risk features.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-35
34471509-2	2021	The Bruton tyrosine kinase inhibitor ibrutinib is one of the approved treatments for symptomatic Waldenstrom macroglobulinemia.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	4-26
34471509-4	2021	Here, we present the case of a patient with Waldenstrom macroglobulinemia with associated acquired von Willebrand syndrome and progressively significant bleeding symptoms, who experienced a rapid increase in von Willebrand factor with ibrutinib treatment, despite only reaching a partial response in IgM levels similar to those reached with other previous treatments.	ibrutinib	235-244	von Willebrand factor	Homo sapiens	208-229
34471509-6	2021	This fact could be explained by the reduced glycoprotein Ib receptor expression induced by ibrutinib and the consequent von Willebrand factor increase in peripheral blood.	ibrutinib	91-100	von Willebrand factor	Homo sapiens	120-141
34153224-1	2021	AIM: We aimed (i) to study the effects of genetic polymorphism of cytochrome P450 3A4 (CYP3A4) and drug interactions on acalabrutinib (ACA) metabolism and (ii) to investigate the mechanisms underlying the effects of CYP3A4 variants on the differential kinetic profiles of ACA and ibrutinib.	ibrutinib	280-289	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	66-85
34153224-1	2021	AIM: We aimed (i) to study the effects of genetic polymorphism of cytochrome P450 3A4 (CYP3A4) and drug interactions on acalabrutinib (ACA) metabolism and (ii) to investigate the mechanisms underlying the effects of CYP3A4 variants on the differential kinetic profiles of ACA and ibrutinib.	ibrutinib	280-289	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	216-222
34424317-1	2021	Although ibrutinib improves the overall survival of patients with chronic lymphocytic leukemia (CLL), some patients still develop resistance, most commonly through point mutations affecting cysteine residue 481 (C481) in Bruton"s tyrosine kinase (BTKC481S and BTKC481R).	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	221-245
34424317-2	2021	To enhance our understanding of the biological impact of these mutations, we established cell lines that overexpress wild-type or mutant BTK in in vitro and in vivo models that mimic ibrutinib-sensitive and -resistant CLL.	ibrutinib	183-192	Bruton tyrosine kinase	Homo sapiens	137-140
34447768-4	2021	Ibrutinib, for example, which was the first BTK inhibitor to be used in clinical trials, has two approved indications, mantle cell lymphoma and chronic lymphocytic leukemia, and remains under evaluation for additional indications.	ibrutinib	0-9	Bruton tyrosine kinase	Canis lupus familiaris	44-47
34426943-5	2021	In the frontline and relapsed settings, we favor ibrutinib monotherapy over chemoimmunotherapy or proteasome inhibitor-based regimens in patients with MYD88 and without CXCR4 mutations.	ibrutinib	49-58	MYD88 innate immune signal transduction adaptor	Homo sapiens	151-156
34540345-2	2021	Bruton"s tyrosine kinase inhibitor ibrutinib represents an effective treatment for R/R MCL patients.	ibrutinib	35-44	Bruton tyrosine kinase	Homo sapiens	0-24
34485307-0	2021	Multifaceted Immunomodulatory Effects of the BTK Inhibitors Ibrutinib and Acalabrutinib on Different Immune Cell Subsets - Beyond B Lymphocytes.	ibrutinib	60-69	Bruton tyrosine kinase	Homo sapiens	45-48
34485307-1	2021	The clinical success of the two BTK inhibitors, ibrutinib and acalabrutinib, represents a major breakthrough in the treatment of chronic lymphocytic leukemia (CLL) and has also revolutionized the treatment options for other B cell malignancies.	ibrutinib	48-57	Bruton tyrosine kinase	Homo sapiens	32-35
34485307-4	2021	The shared and distinct effects of ibrutinib versus acalabrutinib are mediated through BTK-dependent and BTK-independent mechanisms, respectively.	ibrutinib	35-44	Bruton tyrosine kinase	Homo sapiens	87-90
34485307-4	2021	The shared and distinct effects of ibrutinib versus acalabrutinib are mediated through BTK-dependent and BTK-independent mechanisms, respectively.	ibrutinib	35-44	Bruton tyrosine kinase	Homo sapiens	105-108
34127506-0	2021	TP53 disruption in chronic lymphocytic leukemia under ibrutinib: more is worse?	ibrutinib	54-63	tumor protein p53	Homo sapiens	0-4
34127506-1	2021	Chronic lymphocytic leukemia patients carrying a single TP53 hit (chromosome 17p deletion or single TP53 mutation) demonstrate excellent progression-free and overall survival on ibrutinib compared to cases harboring multiple TP53 hits.	ibrutinib	178-187	tumor protein p53	Homo sapiens	56-60
34127506-1	2021	Chronic lymphocytic leukemia patients carrying a single TP53 hit (chromosome 17p deletion or single TP53 mutation) demonstrate excellent progression-free and overall survival on ibrutinib compared to cases harboring multiple TP53 hits.	ibrutinib	178-187	tumor protein p53	Homo sapiens	100-104
34158358-8	2021	One of the three SOX11i, exhibits relatively superior in vitro activity and displays cytotoxic synergy with Ibrutinib in SOX11 expressing MCL cells.	ibrutinib	108-117	SRY-box transcription factor 11	Homo sapiens	121-126
34158358-9	2021	Importantly, this SOX11i induces cytotoxicity specifically in SOX11-positive Ibrutinib-resistant MCL patient samples and inhibits BTK phosphorylation in a xenograft mouse model derived from one of these subjects.	ibrutinib	77-86	SRY-box transcription factor 11	Homo sapiens	62-67
34297159-0	2022	Effect of ibrutinib on CCR7 expression and functionality in chronic lymphocytic leukemia and its implication for the activity of CAP-100, a novel therapeutic anti-CCR7 antibody.	ibrutinib	10-19	C-C motif chemokine receptor 7	Homo sapiens	23-27
34557659-0	2021	The BTK/PI3K/BRD4 axis inhibitor SRX3262 overcomes Ibrutinib resistance in mantle cell lymphoma.	ibrutinib	51-60	Bruton tyrosine kinase	Homo sapiens	4-7
34557659-0	2021	The BTK/PI3K/BRD4 axis inhibitor SRX3262 overcomes Ibrutinib resistance in mantle cell lymphoma.	ibrutinib	51-60	bromodomain containing 4	Homo sapiens	13-17
34557659-3	2021	SRX3262 concomitantly binds to BTK, PI3K, and BRD4, exhibits potent in vitro and in vivo activity against MCL, and overcomes the Ibrutinib resistance resulting from the BTK-C481S mutation.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	169-172
34174982-2	2021	C481S mutation decreases the covalent binding affinity of ibrutinib to BTK, resulting in reversible rather than irreversible inhibition.	ibrutinib	58-67	Bruton tyrosine kinase	Homo sapiens	71-74
34174982-3	2021	In addition to BTK, mutations in PLCG2 have been demonstrated to mediate acquired ibrutinib resistance.	ibrutinib	82-91	phospholipase C gamma 2	Homo sapiens	33-38
34174985-0	2021	Bruton Tyrosine Kinase Inhibitors in Chronic Lymphocytic Leukemia: Beyond Ibrutinib.	ibrutinib	74-83	Bruton tyrosine kinase	Homo sapiens	0-22
34174986-1	2021	The Bruton"s tyrosine kinase inhibitors (BTKis) ibrutinib and acalabrutinib have led to durable responses for patients with both treatment-naive and relapsed/refractory chronic lymphocytic leukemia (CLL).	ibrutinib	48-57	Bruton tyrosine kinase	Homo sapiens	4-28
34297159-0	2022	Effect of ibrutinib on CCR7 expression and functionality in chronic lymphocytic leukemia and its implication for the activity of CAP-100, a novel therapeutic anti-CCR7 antibody.	ibrutinib	10-19	C-C motif chemokine receptor 7	Homo sapiens	163-167
34297159-3	2022	Previous studies, on a very limited number of samples, hypothesized that the Bruton"s tyrosine kinase inhibitor (BTKi) ibrutinib might induce loss of surface CCR7 levels in CLL cells.	ibrutinib	119-128	Bruton tyrosine kinase	Homo sapiens	77-101
34297159-3	2022	Previous studies, on a very limited number of samples, hypothesized that the Bruton"s tyrosine kinase inhibitor (BTKi) ibrutinib might induce loss of surface CCR7 levels in CLL cells.	ibrutinib	119-128	inhibitor of Bruton tyrosine kinase	Homo sapiens	113-117
34297159-3	2022	Previous studies, on a very limited number of samples, hypothesized that the Bruton"s tyrosine kinase inhibitor (BTKi) ibrutinib might induce loss of surface CCR7 levels in CLL cells.	ibrutinib	119-128	C-C motif chemokine receptor 7	Homo sapiens	158-162
34297159-5	2022	As nowadays many relapse/refractory CLL patients will have received ibrutinib as a prior therapy, we aimed to investigate in a large cohort of CLL patients the impact of this BTKi on CCR7 expression and functionality as well as on the therapeutic activity of CAP-100.	ibrutinib	68-77	inhibitor of Bruton tyrosine kinase	Homo sapiens	175-179
34297159-5	2022	As nowadays many relapse/refractory CLL patients will have received ibrutinib as a prior therapy, we aimed to investigate in a large cohort of CLL patients the impact of this BTKi on CCR7 expression and functionality as well as on the therapeutic activity of CAP-100.	ibrutinib	68-77	C-C motif chemokine receptor 7	Homo sapiens	183-187
34297159-6	2022	Our data confirm that ibrutinib moderately down-regulates the very high expression of CCR7 in CLL cells but has no apparent effect on CCR7-induced chemotaxis.	ibrutinib	22-31	C-C motif chemokine receptor 7	Homo sapiens	86-90
34162728-7	2021	Furthermore, activated PTPRG triggers rapid and robust caspase-3/7-mediated apoptosis in CLL cells in a manner quantitatively comparable to the Bruton"s tyrosine kinase inhibitor ibrutinib.	ibrutinib	179-188	Bruton tyrosine kinase	Homo sapiens	144-168
34263144-4	2021	Upon disease progression, novel and targeted agents such as the BTK inhibitor ibrutinib, the BCL-2 inhibitor venetoclax, or the combination of both are increasingly used, but even after allogeneic stem cell transplantation or CAR T-cell therapy, MCL remains incurable for most patients.	ibrutinib	78-87	Bruton tyrosine kinase	Homo sapiens	64-67
34276674-4	2021	Despite having remarkable selectivity for BTK, the first-in-class BTKi ibrutinib can also bind, with various affinities, to other kinases.	ibrutinib	71-80	Bruton tyrosine kinase	Homo sapiens	42-45
34267029-1	2021	In Japan, ibrutinib has been approved as both a front-line and later-line treatment for chronic leukemia/small lymphocytic lymphoma(CLL/SLL).	ibrutinib	10-19	solute carrier family 35 member B2	Homo sapiens	136-139
34267029-4	2021	METHODS: A retrospective cohort study of all patients with CLL/SLL who were treated with ibrutinib at a single institution was conducted.	ibrutinib	89-98	solute carrier family 35 member B2	Homo sapiens	63-66
34276674-4	2021	Despite having remarkable selectivity for BTK, the first-in-class BTKi ibrutinib can also bind, with various affinities, to other kinases.	ibrutinib	71-80	inhibitor of Bruton tyrosine kinase	Homo sapiens	66-70
34249912-7	2021	The first-in-class Ibrutinib and more selective second-generation inhibitors all target the active site of the multidomain BTK protein.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	123-126
34277452-3	2021	Ibrutinib, an oral BTK inhibitor, is a new treatment strategy for CNSL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	19-22
34209188-4	2021	Thus, this study employs structure-based virtual screening (SBVS) to repurpose BTK inhibitors acalabrutinib, dasatinib, evobrutinib, fostamatinib, ibrutinib, inositol 1,3,4,5-tetrakisphosphate, spebrutinib, XL418 and zanubrutinib against SARS-CoV-2.	ibrutinib	147-156	Bruton tyrosine kinase	Homo sapiens	79-82
34174847-1	2021	BACKGROUND: The more selective second-generation BTK inhibitors (BTKi) Acalabrutinib and Zanubrutinib and the first-generation BTKi Ibrutinib are highlighted by their clinical effectiveness in mantle cell lymphoma (MCL), however, similarities and differences of their biological and molecular effects on anti-survival of MCL cells induced by these BTKi with distinct binding selectivity against BTK remain largely unknown.	ibrutinib	132-141	inhibitor of Bruton tyrosine kinase	Homo sapiens	127-131
34174847-1	2021	BACKGROUND: The more selective second-generation BTK inhibitors (BTKi) Acalabrutinib and Zanubrutinib and the first-generation BTKi Ibrutinib are highlighted by their clinical effectiveness in mantle cell lymphoma (MCL), however, similarities and differences of their biological and molecular effects on anti-survival of MCL cells induced by these BTKi with distinct binding selectivity against BTK remain largely unknown.	ibrutinib	132-141	inhibitor of Bruton tyrosine kinase	Homo sapiens	348-352
34174847-1	2021	BACKGROUND: The more selective second-generation BTK inhibitors (BTKi) Acalabrutinib and Zanubrutinib and the first-generation BTKi Ibrutinib are highlighted by their clinical effectiveness in mantle cell lymphoma (MCL), however, similarities and differences of their biological and molecular effects on anti-survival of MCL cells induced by these BTKi with distinct binding selectivity against BTK remain largely unknown.	ibrutinib	132-141	Bruton tyrosine kinase	Homo sapiens	395-398
34174847-7	2021	RESULTS: Acalabrutinib and Zanubrutinib induced moderate apoptosis in Ibrutinib high-sensitive JeKo-1 cells and Ibrutinib low-sensitive Mino cells, which was accompanied by cleaved PARP and caspase-3.	ibrutinib	70-79	collagen type XI alpha 2 chain	Homo sapiens	181-185
34174847-8	2021	Such effects might be caused by the stronger ability of Ibrutinib to upregulate the expression of pro-apoptotic genes, such as HRK, GADD45A, and ATM, in JeKo-1 cells than in Mino cells, and the expression of such apoptotic genes was slightly changed by Acalabrutinib and Zanubrutinib in both JeKo-1 and Mino cells.	ibrutinib	56-65	harakiri, BCL2 interacting protein	Homo sapiens	127-130
34287267-2	2021	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is one of the first-in-class molecules for the treatment of B-CLL patients; however, the emerging mechanisms of resistance to ibrutinib call for new therapeutic strategies.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
34287267-2	2021	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is one of the first-in-class molecules for the treatment of B-CLL patients; however, the emerging mechanisms of resistance to ibrutinib call for new therapeutic strategies.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
34287267-5	2021	In the same setting, combined treatments with ibrutinib plus nutlin-3 led to significantly higher levels of apoptosis compared to the single treatments, counteracting the c-MYC up-regulation.	ibrutinib	46-55	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	171-176
34336499-1	2021	Ibrutinib is a selective Bruton"s tyrosine kinase inhibitor (BTKi) approved for the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	25-49
34336499-1	2021	Ibrutinib is a selective Bruton"s tyrosine kinase inhibitor (BTKi) approved for the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies.	ibrutinib	0-9	inhibitor of Bruton tyrosine kinase	Homo sapiens	61-65
34201565-2	2021	On the basis of several randomised phase III trials showing prolongation of progression-free survival, chemoimmunotherapy is being replaced by treatment based on novel, orally available targeted inhibitors such as Bruton tyrosine kinase inhibitors ibrutinib and acalabrutinib or bcl-2 inhibitor venetoclax.	ibrutinib	248-257	Bruton tyrosine kinase	Homo sapiens	214-236
34174847-8	2021	Such effects might be caused by the stronger ability of Ibrutinib to upregulate the expression of pro-apoptotic genes, such as HRK, GADD45A, and ATM, in JeKo-1 cells than in Mino cells, and the expression of such apoptotic genes was slightly changed by Acalabrutinib and Zanubrutinib in both JeKo-1 and Mino cells.	ibrutinib	56-65	growth arrest and DNA damage inducible alpha	Homo sapiens	132-139
34099830-1	2021	Recent studies suggested that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, developed for the treatment of chronic lymphocytic leukemia, may prevent NLRP3 inflammasome activation in macrophages, IL-1beta secretion and subsequent development of inflammation and organ fibrosis.	ibrutinib	30-39	Bruton tyrosine kinase	Homo sapiens	43-65
34174847-8	2021	Such effects might be caused by the stronger ability of Ibrutinib to upregulate the expression of pro-apoptotic genes, such as HRK, GADD45A, and ATM, in JeKo-1 cells than in Mino cells, and the expression of such apoptotic genes was slightly changed by Acalabrutinib and Zanubrutinib in both JeKo-1 and Mino cells.	ibrutinib	56-65	ATM serine/threonine kinase	Homo sapiens	145-148
34174847-9	2021	Further, Acalabrutinib, Zanubrutinib and Ibrutinib reduced MCL-cell chemotaxis with similar efficiency, due to their similar abilities to downmodulate chemokines, such as CCL3 and CCL4.	ibrutinib	41-50	C-C motif chemokine ligand 3	Homo sapiens	171-175
34174847-9	2021	Further, Acalabrutinib, Zanubrutinib and Ibrutinib reduced MCL-cell chemotaxis with similar efficiency, due to their similar abilities to downmodulate chemokines, such as CCL3 and CCL4.	ibrutinib	41-50	C-C motif chemokine ligand 4	Homo sapiens	180-184
34112701-3	2021	The ITK/Bruton tyrosine kinase inhibitor ibrutinib has been shown to improve chronic GVHD symptoms; however, the effect of ITK selective inhibition on acute GVHD remains unclear.	ibrutinib	41-50	IL2 inducible T cell kinase	Mus musculus	4-7
34112701-3	2021	The ITK/Bruton tyrosine kinase inhibitor ibrutinib has been shown to improve chronic GVHD symptoms; however, the effect of ITK selective inhibition on acute GVHD remains unclear.	ibrutinib	41-50	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	8-30
34164404-6	2021	Notably, the kinase domain is conserved and therefore inhibited by the available BTK-targeting drugs (Ibrutinib, Spebrutinib, etc.)	ibrutinib	102-111	Bruton tyrosine kinase	Homo sapiens	81-84
34099830-1	2021	Recent studies suggested that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, developed for the treatment of chronic lymphocytic leukemia, may prevent NLRP3 inflammasome activation in macrophages, IL-1beta secretion and subsequent development of inflammation and organ fibrosis.	ibrutinib	30-39	Bruton tyrosine kinase	Homo sapiens	67-70
34099830-1	2021	Recent studies suggested that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, developed for the treatment of chronic lymphocytic leukemia, may prevent NLRP3 inflammasome activation in macrophages, IL-1beta secretion and subsequent development of inflammation and organ fibrosis.	ibrutinib	30-39	NLR family pyrin domain containing 3	Homo sapiens	156-161
34099830-1	2021	Recent studies suggested that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, developed for the treatment of chronic lymphocytic leukemia, may prevent NLRP3 inflammasome activation in macrophages, IL-1beta secretion and subsequent development of inflammation and organ fibrosis.	ibrutinib	30-39	interleukin 1 alpha	Homo sapiens	202-210
34099830-3	2021	We therefore hypothesized that the BTK-inhibitor ibrutinib could be a candidate drug for AKI treatment.	ibrutinib	49-58	Bruton tyrosine kinase	Homo sapiens	35-38
34123769-7	2021	We exploited the Isoprenaline-induced intracellular ATP depletion to sensitize primary leukemic cells to fludarabine (purine analogue) and Ibrutinib (Bruton"s tyrosine kinase inhibitor) treatment.	ibrutinib	139-148	Bruton tyrosine kinase	Homo sapiens	150-174
34077419-7	2021	SRMS kinase inhibition activates autophagy, inhibits cancer growth, and can be accomplished using the FDA-approved tyrosine kinase inhibitor ibrutinib.	ibrutinib	141-150	src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites	Homo sapiens	0-4
34150491-4	2021	These patients experienced brief response to ibrutinib, whereas a fourth patient harboring mutated ATM demonstrated a long-term effect to ibrutinib and no CNA.	ibrutinib	138-147	ATM serine/threonine kinase	Homo sapiens	99-102
34239769-2	2021	Ibrutinib is a novel bruton kinase (BTK) inhibitor increasingly used in CLL treatment.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	36-39
34069354-2	2021	Inhibitors of the Bruton tyrosine kinase (BTK), such as ibrutinib or more recently acalabrutinib, are highly effective, even in poor-risk or chemo-refractory patients.	ibrutinib	56-65	Bruton tyrosine kinase	Homo sapiens	18-40
34069354-2	2021	Inhibitors of the Bruton tyrosine kinase (BTK), such as ibrutinib or more recently acalabrutinib, are highly effective, even in poor-risk or chemo-refractory patients.	ibrutinib	56-65	Bruton tyrosine kinase	Homo sapiens	42-45
34065833-5	2021	Ibrutinib, through ITK-driven Th1 polarization of cell-mediated immune response, is known to produce an immunological rebalancing in CLL, which stands as a fascinating rationale for its use to treat autoimmunity.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	19-22
34123480-3	2021	Currently, there are three BTK inhibitors approved by the U.S. Food and Drug Administration: ibrutinib, acalabrutinib, and zanubrutinib.	ibrutinib	93-102	Bruton tyrosine kinase	Homo sapiens	27-30
35608822-1	2022	PURPOSE: Dual blockade of Bruton"s tyrosine kinase with ibrutinib and selinexor has potential to deepen responses for patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL).	ibrutinib	56-65	Bruton tyrosine kinase	Homo sapiens	26-50
35597428-9	2022	Moreover, in CLL samples, inhibition of RAC, which can mediate BTK-independent activation of PLCgamma2, cooperated with ibrutinib to suppress calcium responses.	ibrutinib	120-129	Bruton tyrosine kinase	Homo sapiens	63-66
35597428-9	2022	Moreover, in CLL samples, inhibition of RAC, which can mediate BTK-independent activation of PLCgamma2, cooperated with ibrutinib to suppress calcium responses.	ibrutinib	120-129	phospholipase C gamma 2	Homo sapiens	93-102
35377947-2	2022	Here we report extended long-term follow-up from the RESONATE-2 phase 3 study of the once-daily Bruton"s tyrosine kinase inhibitor ibrutinib, which is the only targeted therapy with significant progression-free survival (PFS) and overall survival (OS) benefit in multiple randomized phase 3 CLL studies.	ibrutinib	131-140	Bruton tyrosine kinase	Homo sapiens	96-120
35377947-6	2022	PFS benefit was also observed for ibrutinib- versus chlorambucil-randomized patients with high-risk genomic features: del(11q) (HR 0.033 (95% CI: 0.010-0.107)) or unmutated IGHV (HR 0.112 (95% CI: 0.065-0.192)).	ibrutinib	34-43	immunoglobulin heavy variable 3-69-1 (pseudogene)	Homo sapiens	173-177
35357653-3	2022	Ibrutinib was the first BTK inhibitor approved for clinical use, and showed excellent efficacy and an acceptable safety profile.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	24-27
35577568-1	2022	OBJECTIVES: Ibrutinib is active in anti-myelin-associated glycoprotein (MAG) polyneuropathy with MYD88L265P mutation; however, its efficacy is likely to be low in MYD88 wild-type patients.	ibrutinib	12-21	myelin associated glycoprotein	Homo sapiens	40-70
35595730-7	2022	In vitro incubations of CLL cells harboring wild-type or mutant BTK had inhibition of the BCR pathway with either ibrutinib or pirtobrutinib treatment.	ibrutinib	114-123	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	64-67
35393988-6	2022	In this study, a biocompatible, tumor-targeting, on-demand approach combining CAR-T cell immunotherapy and a chemo-photothermal therapy nanoplatform (FA-Gd-GERTs@Ibrutinib) based on gadolinium-loaded gap-enhanced Raman tags (Gd-GERTs) has been developed for multimodal imaging, and it provides a reliable treatment strategy for solid tumor immunotherapy via microenvironment reconstruction.	ibrutinib	162-171	nuclear receptor subfamily 1, group I, member 3	Mus musculus	78-81
35587148-5	2022	Using the scaffold of the Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib for our proof-of-concept, we reasoned that increasing the steric bulk of fumarate-based electrophiles on Ibrutinib should improve selectivity via the steric exclusion of off-targets but retain rates of cysteine reactivity comparable to that of an acrylamide.	ibrutinib	67-76	Bruton tyrosine kinase	Homo sapiens	26-50
35587148-5	2022	Using the scaffold of the Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib for our proof-of-concept, we reasoned that increasing the steric bulk of fumarate-based electrophiles on Ibrutinib should improve selectivity via the steric exclusion of off-targets but retain rates of cysteine reactivity comparable to that of an acrylamide.	ibrutinib	67-76	Bruton tyrosine kinase	Homo sapiens	52-55
35587148-5	2022	Using the scaffold of the Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib for our proof-of-concept, we reasoned that increasing the steric bulk of fumarate-based electrophiles on Ibrutinib should improve selectivity via the steric exclusion of off-targets but retain rates of cysteine reactivity comparable to that of an acrylamide.	ibrutinib	182-191	Bruton tyrosine kinase	Homo sapiens	26-50
35587148-5	2022	Using the scaffold of the Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib for our proof-of-concept, we reasoned that increasing the steric bulk of fumarate-based electrophiles on Ibrutinib should improve selectivity via the steric exclusion of off-targets but retain rates of cysteine reactivity comparable to that of an acrylamide.	ibrutinib	182-191	Bruton tyrosine kinase	Homo sapiens	52-55
35587148-11	2022	Of these 8 proteins, 7 are also downregulated by Ibrutinib and a majority of these targets are associated with BTK biology.	ibrutinib	49-58	Bruton tyrosine kinase	Homo sapiens	111-114
35628931-4	2022	Ibrutinib is the first covalent, irreversible BTK inhibitor approved in 2013 as a breakthrough therapy for chronic lymphocytic leukemia patients.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	46-49
35577568-1	2022	OBJECTIVES: Ibrutinib is active in anti-myelin-associated glycoprotein (MAG) polyneuropathy with MYD88L265P mutation; however, its efficacy is likely to be low in MYD88 wild-type patients.	ibrutinib	12-21	MYD88 innate immune signal transduction adaptor	Homo sapiens	163-168
35571529-3	2022	BTK inhibitor ibrutinib, in particular, has demonstrated improvement in survival outcomes of R/R MCL.	ibrutinib	14-23	Bruton tyrosine kinase	Homo sapiens	0-3
35533307-8	2022	Implications: This phosphoproteomic analysis and functional validation illuminated the phosphorylation of KAP1 at S473 as an important downstream BCR signaling event and a potential indicator for the success of ibrutinib treatment in CLL.	ibrutinib	211-220	tripartite motif containing 28	Homo sapiens	106-110
35573643-6	2022	Results and Conclusions: Platelet activation and downstream signaling were abolished in murine and human platelets in the presence of the Btk inhibitors ibrutinib or acalabrutinib when a low concentration of a CLEC-2 antibody was used to crosslink CLEC-2 receptors.	ibrutinib	153-162	Bruton tyrosine kinase	Homo sapiens	138-141
35573643-6	2022	Results and Conclusions: Platelet activation and downstream signaling were abolished in murine and human platelets in the presence of the Btk inhibitors ibrutinib or acalabrutinib when a low concentration of a CLEC-2 antibody was used to crosslink CLEC-2 receptors.	ibrutinib	153-162	C-type lectin domain family 1 member B	Homo sapiens	248-254
35404729-2	2022	Ibrutinib was the first BTK inhibitor to receive FDA approval for this disease, but in recent years additional more selective BTK inhibitors have become available.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	24-27
35194155-0	2022	Successful treatment of refractory pure red cell aplasia in major ABO-mismatched allogeneic hematopoietic stem cell transplant with single agent Ibrutinib.	ibrutinib	145-154	ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase	Homo sapiens	66-69
35352453-5	2022	By using in vitro and in vivo models of primary and secondary ibrutinib resistance as well as post-ibrutinib treatment clinical samples, we show that dual targeting of the BCL-2 and PI3-kinase signalling pathways results in synergistic anti-tumour activity.	ibrutinib	62-71	BCL2 apoptosis regulator	Homo sapiens	172-177
35352453-5	2022	By using in vitro and in vivo models of primary and secondary ibrutinib resistance as well as post-ibrutinib treatment clinical samples, we show that dual targeting of the BCL-2 and PI3-kinase signalling pathways results in synergistic anti-tumour activity.	ibrutinib	99-108	BCL2 apoptosis regulator	Homo sapiens	172-177
35266562-6	2022	Molecular mechanism of resistance, mutation dynamics and pathogenic pathways (BCR, oxidative phosphorylation and MYC) were identified in mediating resistance to various treatments (BTK inhibitors (ibrutinib, acalabrutinib).	ibrutinib	197-206	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	113-116
35507054-2	2022	Currently, there are 3 BTK inhibitors available to treat CLL: ibrutinib, acalabrutinib, and zanubrutinib (the latter not yet approved for this disease but included in the NCCN guidelines).	ibrutinib	62-71	Bruton tyrosine kinase	Homo sapiens	23-26
35476648-1	2022	Ibrutinib and acalabrutinib are Bruton"s tyrosine kinase inhibitors (BTKis) that are effective therapies for chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	32-56
35484253-0	2022	Richter"s syndrome in central nervous system with MYD88L265P and CD79b mutation responded well to ibrutinib containing chemotherapy: a case report and review of the literature.	ibrutinib	98-107	MYD88 innate immune signal transduction adaptor	Homo sapiens	50-55
35484253-0	2022	Richter"s syndrome in central nervous system with MYD88L265P and CD79b mutation responded well to ibrutinib containing chemotherapy: a case report and review of the literature.	ibrutinib	98-107	CD79b molecule	Homo sapiens	65-70
35629099-4	2022	The first BTKi to receive US Food and Drug Administration approval for WM was ibrutinib.	ibrutinib	78-87	inhibitor of Bruton tyrosine kinase	Homo sapiens	10-14
35591835-0	2022	Ibrutinib attenuated DSS-induced ulcerative colitis, oxidative stress, and the inflammatory cascade by modulating the PI3K/Akt and JNK/NF-kappaB pathways.	ibrutinib	0-9	AKT serine/threonine kinase 1	Homo sapiens	123-126
35591835-0	2022	Ibrutinib attenuated DSS-induced ulcerative colitis, oxidative stress, and the inflammatory cascade by modulating the PI3K/Akt and JNK/NF-kappaB pathways.	ibrutinib	0-9	mitogen-activated protein kinase 8	Homo sapiens	131-134
35591835-0	2022	Ibrutinib attenuated DSS-induced ulcerative colitis, oxidative stress, and the inflammatory cascade by modulating the PI3K/Akt and JNK/NF-kappaB pathways.	ibrutinib	0-9	nuclear factor kappa B subunit 1	Homo sapiens	135-144
35611166-0	2022	Ibrutinib Inhibits BMX-Dependent Endothelial VCAM-1 Expression In Vitro and Pro-Atherosclerotic Endothelial Activation and Platelet Adhesion In Vivo.	ibrutinib	0-9	BMX non-receptor tyrosine kinase	Homo sapiens	19-22
35514998-5	2022	She fulfilled the diagnosis of Schnitzler syndrome and was treated with the Bruton tyrosine kinase inhibitor ibrutinib in combination with prednisone.	ibrutinib	109-118	Bruton tyrosine kinase	Homo sapiens	76-98
35440579-1	2022	The clinical introduction of the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, which targets B-cell antigen-receptor (BCR)-controlled integrin-mediated retention of malignant B cells in their growth-supportive lymphoid organ microenvironment, provided a major breakthrough in lymphoma and leukemia treatment.	ibrutinib	74-83	Bruton tyrosine kinase	Homo sapiens	33-57
35440579-1	2022	The clinical introduction of the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, which targets B-cell antigen-receptor (BCR)-controlled integrin-mediated retention of malignant B cells in their growth-supportive lymphoid organ microenvironment, provided a major breakthrough in lymphoma and leukemia treatment.	ibrutinib	74-83	Bruton tyrosine kinase	Homo sapiens	59-62
35440579-1	2022	The clinical introduction of the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, which targets B-cell antigen-receptor (BCR)-controlled integrin-mediated retention of malignant B cells in their growth-supportive lymphoid organ microenvironment, provided a major breakthrough in lymphoma and leukemia treatment.	ibrutinib	74-83	BCR activator of RhoGEF and GTPase	Homo sapiens	99-122
35440579-1	2022	The clinical introduction of the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, which targets B-cell antigen-receptor (BCR)-controlled integrin-mediated retention of malignant B cells in their growth-supportive lymphoid organ microenvironment, provided a major breakthrough in lymphoma and leukemia treatment.	ibrutinib	74-83	BCR activator of RhoGEF and GTPase	Homo sapiens	124-127
35465824-3	2022	Following evidence showing the expression of BTK on many hematopoietic cells (an exception beting T lymphocytes) has given rise to the idea that inhibition of BTK with BTK inhibitors (BTKi) such as ibrutinib can help treat CLL.As BTK has a wide variation of expression among cells the use of BTKi has been shown to not only control CLL clones but also redistribute the balance of humoral immunity back toward those of healthy control.	ibrutinib	198-207	Bruton tyrosine kinase	Homo sapiens	45-48
35465824-3	2022	Following evidence showing the expression of BTK on many hematopoietic cells (an exception beting T lymphocytes) has given rise to the idea that inhibition of BTK with BTK inhibitors (BTKi) such as ibrutinib can help treat CLL.As BTK has a wide variation of expression among cells the use of BTKi has been shown to not only control CLL clones but also redistribute the balance of humoral immunity back toward those of healthy control.	ibrutinib	198-207	Bruton tyrosine kinase	Homo sapiens	159-162
35465824-3	2022	Following evidence showing the expression of BTK on many hematopoietic cells (an exception beting T lymphocytes) has given rise to the idea that inhibition of BTK with BTK inhibitors (BTKi) such as ibrutinib can help treat CLL.As BTK has a wide variation of expression among cells the use of BTKi has been shown to not only control CLL clones but also redistribute the balance of humoral immunity back toward those of healthy control.	ibrutinib	198-207	Bruton tyrosine kinase	Homo sapiens	168-171
35465824-3	2022	Following evidence showing the expression of BTK on many hematopoietic cells (an exception beting T lymphocytes) has given rise to the idea that inhibition of BTK with BTK inhibitors (BTKi) such as ibrutinib can help treat CLL.As BTK has a wide variation of expression among cells the use of BTKi has been shown to not only control CLL clones but also redistribute the balance of humoral immunity back toward those of healthy control.	ibrutinib	198-207	inhibitor of Bruton tyrosine kinase	Homo sapiens	184-188
35465824-3	2022	Following evidence showing the expression of BTK on many hematopoietic cells (an exception beting T lymphocytes) has given rise to the idea that inhibition of BTK with BTK inhibitors (BTKi) such as ibrutinib can help treat CLL.As BTK has a wide variation of expression among cells the use of BTKi has been shown to not only control CLL clones but also redistribute the balance of humoral immunity back toward those of healthy control.	ibrutinib	198-207	Bruton tyrosine kinase	Homo sapiens	230-233
35465824-3	2022	Following evidence showing the expression of BTK on many hematopoietic cells (an exception beting T lymphocytes) has given rise to the idea that inhibition of BTK with BTK inhibitors (BTKi) such as ibrutinib can help treat CLL.As BTK has a wide variation of expression among cells the use of BTKi has been shown to not only control CLL clones but also redistribute the balance of humoral immunity back toward those of healthy control.	ibrutinib	198-207	inhibitor of Bruton tyrosine kinase	Homo sapiens	292-296
35443042-7	2022	There are currently 3 FDA approvals for the treatment of chronic GVHD: (1) ibrutinib, a BTK inhibitor traditionally used for B-cell malignancies, was the first agent approved for chronic GVHD after failure of one or more lines of systemic therapy, (2) belumosudil, an oral selective inhibitor of ROCK2, for patients with chronic GVHD who received at least 2 prior lines of treatment, and (3) ruxolitinib for chronic GVHD after failure of one or two lines of systemic therapy.	ibrutinib	75-84	Bruton tyrosine kinase	Homo sapiens	88-91
35443042-7	2022	There are currently 3 FDA approvals for the treatment of chronic GVHD: (1) ibrutinib, a BTK inhibitor traditionally used for B-cell malignancies, was the first agent approved for chronic GVHD after failure of one or more lines of systemic therapy, (2) belumosudil, an oral selective inhibitor of ROCK2, for patients with chronic GVHD who received at least 2 prior lines of treatment, and (3) ruxolitinib for chronic GVHD after failure of one or two lines of systemic therapy.	ibrutinib	75-84	Rho associated coiled-coil containing protein kinase 2	Homo sapiens	296-301
35611166-0	2022	Ibrutinib Inhibits BMX-Dependent Endothelial VCAM-1 Expression In Vitro and Pro-Atherosclerotic Endothelial Activation and Platelet Adhesion In Vivo.	ibrutinib	0-9	vascular cell adhesion molecule 1	Homo sapiens	45-51
35611166-4	2022	Methods and Results: In vitro, we found that ibrutinib blocked activation of the TFK member, BMX, by vascular endothelial growth factors (VEGF)-A in human aortic endothelial cells (HAECs).	ibrutinib	45-54	BMX non-receptor tyrosine kinase	Homo sapiens	93-96
35611166-4	2022	Methods and Results: In vitro, we found that ibrutinib blocked activation of the TFK member, BMX, by vascular endothelial growth factors (VEGF)-A in human aortic endothelial cells (HAECs).	ibrutinib	45-54	vascular endothelial growth factor A	Homo sapiens	138-145
35611166-5	2022	Blockade of BMX activation with ibrutinib or pharmacologically distinct BMX inhibitors eliminated the ability of VEGF-A to stimulate VCAM-1 expression in HAECs.	ibrutinib	32-41	BMX non-receptor tyrosine kinase	Homo sapiens	12-15
35611166-5	2022	Blockade of BMX activation with ibrutinib or pharmacologically distinct BMX inhibitors eliminated the ability of VEGF-A to stimulate VCAM-1 expression in HAECs.	ibrutinib	32-41	vascular cell adhesion molecule 1	Homo sapiens	133-139
35611166-9	2022	Conclusion: Herein we found that VEGF-A signals through BMX to induce VCAM-1 expression in endothelial cells, and that VCAM-1 expression is sensitive to ibrutinib in vitro and in atherosclerosis-prone carotid arteries in vivo.	ibrutinib	153-162	vascular endothelial growth factor A	Homo sapiens	33-39
35611166-9	2022	Conclusion: Herein we found that VEGF-A signals through BMX to induce VCAM-1 expression in endothelial cells, and that VCAM-1 expression is sensitive to ibrutinib in vitro and in atherosclerosis-prone carotid arteries in vivo.	ibrutinib	153-162	vascular cell adhesion molecule 1	Homo sapiens	119-125
35450208-9	2022	Preclinical and recent clinical data showed an efficacy of ibrutinib, a BTK inhibitor (BTKi), in HCL and HCL-V.	ibrutinib	59-68	inhibitor of Bruton tyrosine kinase	Homo sapiens	87-91
35427411-11	2022	In conclusion, Ibrutinib-rituximab therapy offers superior PFS relative to FCR in both IGHV mutated and unmutated CLL patients as well as superior OS.	ibrutinib	15-24	immunoglobulin heavy variable 3-69-1 (pseudogene)	Homo sapiens	87-91
35456016-2	2022	In recent years, ibrutinib, an oral BTK inhibitor, became a breakthrough therapy for hematological malignancies, such as chronic lymphocytic.	ibrutinib	17-26	Bruton tyrosine kinase	Homo sapiens	36-39
35456016-6	2022	Consequently, ibrutinib, a BTK-inhibitor, has been studied as a therapeutic option in solid malignancies.	ibrutinib	14-23	Bruton tyrosine kinase	Homo sapiens	27-30
35456016-8	2022	Nevertheless, while ibrutinib failed as a monotherapy, it might become an interesting part of a multidrug regime: not only has a synergism between ibrutinib and other compounds, such as trametinib or dactolisib, been observed in vitro, but this BTK inhibitor has also been established as a radio- and chemosensitizer.	ibrutinib	20-29	Bruton tyrosine kinase	Homo sapiens	245-248
35456016-8	2022	Nevertheless, while ibrutinib failed as a monotherapy, it might become an interesting part of a multidrug regime: not only has a synergism between ibrutinib and other compounds, such as trametinib or dactolisib, been observed in vitro, but this BTK inhibitor has also been established as a radio- and chemosensitizer.	ibrutinib	147-156	Bruton tyrosine kinase	Homo sapiens	245-248
35410313-7	2022	Combinational therapies with rituximab-ibrutinib, rituximab-venetoclax and rituximab-CHOP also induced CD20 internalization which was again effectively blocked by BI-1206.	ibrutinib	39-48	keratin 20	Homo sapiens	103-107
35437106-0	2022	Cardiotoxicity of BTK inhibitors: ibrutinib and beyond.	ibrutinib	34-43	Bruton tyrosine kinase	Homo sapiens	18-21
35379357-2	2022	The first-in-class BTK inhibitor ibrutinib has shown remarkable therapeutic effects and manageable toxicities in multiple clinical trials.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	19-22
35493119-2	2022	Ibrutinib, a once-daily Bruton tyrosine kinase inhibitor, may mitigate COVID-19-induced lung damage by reducing inflammatory cytokines.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	24-46
35247800-2	2022	The Btk inhibitor ibrutinib has been shown to selectively block platelet adhesion to atherosclerotic plaque material under laminar arterial flow.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
35247800-10	2022	CONCLUSION: Treatment of patients with haematological disorders with the Btk inhibitor ibrutinib reduces in vitro platelet deposition, thrombus size and contraction on human atherosclerotic plaque around a stenosis when compared to patients not receiving ibrutinib.	ibrutinib	87-96	Bruton tyrosine kinase	Homo sapiens	73-76
35406532-2	2022	The Bruton tyrosine kinase inhibitor ibrutinib, given as monotherapy or combined with other molecules, has proven effective in numerous B-cell lymphomas.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	4-26
35454970-9	2022	Blockade of IL-1 with drugs such as canakinumab and anakinra, and inhibition of Bruton tyrosine kinase (BTK) with zanubrutinib and ibrutinib was also beneficial.	ibrutinib	131-140	Bruton tyrosine kinase	Homo sapiens	80-102
35454970-9	2022	Blockade of IL-1 with drugs such as canakinumab and anakinra, and inhibition of Bruton tyrosine kinase (BTK) with zanubrutinib and ibrutinib was also beneficial.	ibrutinib	131-140	Bruton tyrosine kinase	Homo sapiens	104-107
35496952-3	2022	Ibrutinib is one of these treatments and acts by inhibiting bruton tyrosine kinase.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	60-82
35349631-2	2022	Preclinical data suggesting synergy between CART-19 and the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib prompted us to conduct a prospective single-center phase 2 trial in which we added autologous anti-CD19 humanized binding domain T cells (huCART-19) to ibrutinib in CLL patients not in CR despite at least 6 months of ibrutinib.	ibrutinib	101-110	Bruton tyrosine kinase	Homo sapiens	60-84
35349631-2	2022	Preclinical data suggesting synergy between CART-19 and the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib prompted us to conduct a prospective single-center phase 2 trial in which we added autologous anti-CD19 humanized binding domain T cells (huCART-19) to ibrutinib in CLL patients not in CR despite at least 6 months of ibrutinib.	ibrutinib	101-110	Bruton tyrosine kinase	Homo sapiens	86-89
35179349-3	2022	Herein, a tumor immune-microenvironment reshaped hybrid nanocage CPN-NLI/MLD coloaded with the Bruton"s tyrosine kinase inhibitor ibrutinib, and cytotoxic drug docetaxel was developed for stepwise targeting TIBs and tumor cells, respectively.	ibrutinib	130-139	LIM domain binding 1	Homo sapiens	69-72
35179349-3	2022	Herein, a tumor immune-microenvironment reshaped hybrid nanocage CPN-NLI/MLD coloaded with the Bruton"s tyrosine kinase inhibitor ibrutinib, and cytotoxic drug docetaxel was developed for stepwise targeting TIBs and tumor cells, respectively.	ibrutinib	130-139	Bruton tyrosine kinase	Homo sapiens	95-119
35179349-7	2022	Targeting of ibrutinib to TIBs was achieved by the interaction of Neu5Ac modified on inner ibrutinib-particle NLI and CD22 on the surface of TIBs.	ibrutinib	13-22	LIM domain binding 1	Homo sapiens	110-113
35179349-7	2022	Targeting of ibrutinib to TIBs was achieved by the interaction of Neu5Ac modified on inner ibrutinib-particle NLI and CD22 on the surface of TIBs.	ibrutinib	13-22	CD22 molecule	Homo sapiens	118-122
35448150-0	2022	Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma: Results of the Proof-of-Concept iMYC Study.	ibrutinib	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	13-18
35448150-2	2022	c-MYC and/or HER-2 amplified oesophageal cancer models have demonstrated sensitivity to BTK inhibition with ibrutinib.	ibrutinib	108-117	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	0-5
35448150-2	2022	c-MYC and/or HER-2 amplified oesophageal cancer models have demonstrated sensitivity to BTK inhibition with ibrutinib.	ibrutinib	108-117	erb-b2 receptor tyrosine kinase 2	Homo sapiens	13-18
35179349-7	2022	Targeting of ibrutinib to TIBs was achieved by the interaction of Neu5Ac modified on inner ibrutinib-particle NLI and CD22 on the surface of TIBs.	ibrutinib	91-100	LIM domain binding 1	Homo sapiens	110-113
35448150-2	2022	c-MYC and/or HER-2 amplified oesophageal cancer models have demonstrated sensitivity to BTK inhibition with ibrutinib.	ibrutinib	108-117	Bruton tyrosine kinase	Homo sapiens	88-91
35179349-8	2022	The boosted antitumor immunity was achieved mainly by the inhibition of Bruton"s tyrosine kinase activation mediated by ibrutinib, which reduced the proportion of TIBs, enhanced infiltration of CD8+ and CD4+ T cells, increased the secretion of immunogenic cytokines including IL-2 and IFN-gamma, and inhibited the proliferation of regulatory T cells and secretion of immunosuppressive cytokines including IL-10, IL-4, and TGF-beta.	ibrutinib	120-129	Bruton tyrosine kinase	Homo sapiens	72-96
35448150-3	2022	We evaluated the safety and efficacy of ibrutinib in patients with c-MYC and/or HER2 amplified pre-treated advanced OG cancer.	ibrutinib	40-49	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	67-72
35179349-8	2022	The boosted antitumor immunity was achieved mainly by the inhibition of Bruton"s tyrosine kinase activation mediated by ibrutinib, which reduced the proportion of TIBs, enhanced infiltration of CD8+ and CD4+ T cells, increased the secretion of immunogenic cytokines including IL-2 and IFN-gamma, and inhibited the proliferation of regulatory T cells and secretion of immunosuppressive cytokines including IL-10, IL-4, and TGF-beta.	ibrutinib	120-129	CD8a molecule	Homo sapiens	194-197
35179349-8	2022	The boosted antitumor immunity was achieved mainly by the inhibition of Bruton"s tyrosine kinase activation mediated by ibrutinib, which reduced the proportion of TIBs, enhanced infiltration of CD8+ and CD4+ T cells, increased the secretion of immunogenic cytokines including IL-2 and IFN-gamma, and inhibited the proliferation of regulatory T cells and secretion of immunosuppressive cytokines including IL-10, IL-4, and TGF-beta.	ibrutinib	120-129	CD4 molecule	Homo sapiens	203-206
35179349-8	2022	The boosted antitumor immunity was achieved mainly by the inhibition of Bruton"s tyrosine kinase activation mediated by ibrutinib, which reduced the proportion of TIBs, enhanced infiltration of CD8+ and CD4+ T cells, increased the secretion of immunogenic cytokines including IL-2 and IFN-gamma, and inhibited the proliferation of regulatory T cells and secretion of immunosuppressive cytokines including IL-10, IL-4, and TGF-beta.	ibrutinib	120-129	interleukin 2	Homo sapiens	276-280
35179349-8	2022	The boosted antitumor immunity was achieved mainly by the inhibition of Bruton"s tyrosine kinase activation mediated by ibrutinib, which reduced the proportion of TIBs, enhanced infiltration of CD8+ and CD4+ T cells, increased the secretion of immunogenic cytokines including IL-2 and IFN-gamma, and inhibited the proliferation of regulatory T cells and secretion of immunosuppressive cytokines including IL-10, IL-4, and TGF-beta.	ibrutinib	120-129	interferon gamma	Homo sapiens	285-294
35179349-8	2022	The boosted antitumor immunity was achieved mainly by the inhibition of Bruton"s tyrosine kinase activation mediated by ibrutinib, which reduced the proportion of TIBs, enhanced infiltration of CD8+ and CD4+ T cells, increased the secretion of immunogenic cytokines including IL-2 and IFN-gamma, and inhibited the proliferation of regulatory T cells and secretion of immunosuppressive cytokines including IL-10, IL-4, and TGF-beta.	ibrutinib	120-129	interleukin 10	Homo sapiens	405-410
35179349-8	2022	The boosted antitumor immunity was achieved mainly by the inhibition of Bruton"s tyrosine kinase activation mediated by ibrutinib, which reduced the proportion of TIBs, enhanced infiltration of CD8+ and CD4+ T cells, increased the secretion of immunogenic cytokines including IL-2 and IFN-gamma, and inhibited the proliferation of regulatory T cells and secretion of immunosuppressive cytokines including IL-10, IL-4, and TGF-beta.	ibrutinib	120-129	interleukin 4	Homo sapiens	412-416
35179349-8	2022	The boosted antitumor immunity was achieved mainly by the inhibition of Bruton"s tyrosine kinase activation mediated by ibrutinib, which reduced the proportion of TIBs, enhanced infiltration of CD8+ and CD4+ T cells, increased the secretion of immunogenic cytokines including IL-2 and IFN-gamma, and inhibited the proliferation of regulatory T cells and secretion of immunosuppressive cytokines including IL-10, IL-4, and TGF-beta.	ibrutinib	120-129	transforming growth factor alpha	Homo sapiens	422-430
35296194-1	2022	INTRODUCTION: : The first-in-class Bruton tyrosine kinase (BTK), ibrutinib, demonstrated remarkable activity in chronic lymphocytic leukemia (CLL).	ibrutinib	65-74	Bruton tyrosine kinase	Homo sapiens	35-57
35326604-5	2022	Moreover, a number of targeted agents, especially the Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib, seem to have activity in certain patient subsets in 1L and are currently being tested in front-line regimens.	ibrutinib	95-104	Bruton tyrosine kinase	Homo sapiens	54-78
35326604-5	2022	Moreover, a number of targeted agents, especially the Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib, seem to have activity in certain patient subsets in 1L and are currently being tested in front-line regimens.	ibrutinib	95-104	Bruton tyrosine kinase	Homo sapiens	80-83
35449638-1	2022	Ibrutinib is an irreversible Bruton tyrosine kinase inhibitor that is approved for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenstrom macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	29-51
35296194-1	2022	INTRODUCTION: : The first-in-class Bruton tyrosine kinase (BTK), ibrutinib, demonstrated remarkable activity in chronic lymphocytic leukemia (CLL).	ibrutinib	65-74	Bruton tyrosine kinase	Homo sapiens	59-62
35197546-0	2022	Ibrutinib reverses IL-6-induced osimertinib resistance through inhibition of Laminin alpha5/FAK signaling.	ibrutinib	0-9	interleukin 6	Homo sapiens	19-23
35227147-1	2022	Joint and muscle pain, including arthralgia, myalgia, and musculoskeletal pain, are among the common adverse events (AEs) reported for ibrutinib, a once-daily Bruton"s tyrosine kinase inhibitor approved for the treatment of various B-cell malignancies, including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).	ibrutinib	135-144	Bruton tyrosine kinase	Homo sapiens	159-183
35197546-0	2022	Ibrutinib reverses IL-6-induced osimertinib resistance through inhibition of Laminin alpha5/FAK signaling.	ibrutinib	0-9	protein tyrosine kinase 2	Homo sapiens	77-95
35197546-7	2022	Next, using a large-scale compound screening, we identify ibrutinib as a potent inhibitor of IL-6 and Laminin alpha5/FAK signaling, which shows synergy with osimertinib in osimertinib-resistant cells with high IL-6 levels, but not in those with low IL-6 levels.	ibrutinib	58-67	interleukin 6	Homo sapiens	93-97
35197546-7	2022	Next, using a large-scale compound screening, we identify ibrutinib as a potent inhibitor of IL-6 and Laminin alpha5/FAK signaling, which shows synergy with osimertinib in osimertinib-resistant cells with high IL-6 levels, but not in those with low IL-6 levels.	ibrutinib	58-67	protein tyrosine kinase 2	Homo sapiens	102-120
35197546-7	2022	Next, using a large-scale compound screening, we identify ibrutinib as a potent inhibitor of IL-6 and Laminin alpha5/FAK signaling, which shows synergy with osimertinib in osimertinib-resistant cells with high IL-6 levels, but not in those with low IL-6 levels.	ibrutinib	58-67	interleukin 6	Homo sapiens	210-214
35197546-7	2022	Next, using a large-scale compound screening, we identify ibrutinib as a potent inhibitor of IL-6 and Laminin alpha5/FAK signaling, which shows synergy with osimertinib in osimertinib-resistant cells with high IL-6 levels, but not in those with low IL-6 levels.	ibrutinib	58-67	interleukin 6	Homo sapiens	249-253
35197546-9	2022	Taken together, we conclude that Laminin alpha5/FAK signaling is responsible for IL-6-induced osimertinib resistance, which could be reversed by combination of ibrutinib and osimertinib.	ibrutinib	160-169	protein tyrosine kinase 2	Homo sapiens	33-51
35197546-9	2022	Taken together, we conclude that Laminin alpha5/FAK signaling is responsible for IL-6-induced osimertinib resistance, which could be reversed by combination of ibrutinib and osimertinib.	ibrutinib	160-169	interleukin 6	Homo sapiens	81-85
35188143-1	2022	Ibrutinib, an oral small-molecule targeted drug, has been the first Bruton tyrosine kinase (BTK) inhibitor in the world to be approved for the market.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	68-90
35243171-7	2022	This case demonstrates an association between Ibrutinib an oral, irreversible inhibitor of Bruton"s Tyrosine Kinase (BTK), and the development of CME.	ibrutinib	46-55	Bruton tyrosine kinase	Homo sapiens	91-115
35243171-7	2022	This case demonstrates an association between Ibrutinib an oral, irreversible inhibitor of Bruton"s Tyrosine Kinase (BTK), and the development of CME.	ibrutinib	46-55	Bruton tyrosine kinase	Homo sapiens	117-120
35159041-4	2022	Ibrutinib was the first irreversible BTK inhibitor approved by the U.S. Food and Drug Administration in 2013 as a breakthrough therapy in CLL patients.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	37-40
35159041-6	2022	Two other irreversible, second-generation BTK inhibitors, acalabrutinib and zanubrutinib, were developed to reduce ibrutinib-mediated adverse effects.	ibrutinib	115-124	Bruton tyrosine kinase	Homo sapiens	42-45
34706199-10	2022	Cd38 /  macrophages displayed markedly increased activation of Btk, NF-KappaB, and NLRP3 whereas in vivo administration of the Btk inhibitor ibrutinib (a FDA approved drug) prevented augmented TLR4-induced inflammatory lung injury seen in Cd38 /  mice.	ibrutinib	141-150	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	63-66
34706199-10	2022	Cd38 /  macrophages displayed markedly increased activation of Btk, NF-KappaB, and NLRP3 whereas in vivo administration of the Btk inhibitor ibrutinib (a FDA approved drug) prevented augmented TLR4-induced inflammatory lung injury seen in Cd38 /  mice.	ibrutinib	141-150	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	68-77
35188143-1	2022	Ibrutinib, an oral small-molecule targeted drug, has been the first Bruton tyrosine kinase (BTK) inhibitor in the world to be approved for the market.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	92-95
34706199-10	2022	Cd38 /  macrophages displayed markedly increased activation of Btk, NF-KappaB, and NLRP3 whereas in vivo administration of the Btk inhibitor ibrutinib (a FDA approved drug) prevented augmented TLR4-induced inflammatory lung injury seen in Cd38 /  mice.	ibrutinib	141-150	NLR family, pyrin domain containing 3	Mus musculus	83-88
34706199-10	2022	Cd38 /  macrophages displayed markedly increased activation of Btk, NF-KappaB, and NLRP3 whereas in vivo administration of the Btk inhibitor ibrutinib (a FDA approved drug) prevented augmented TLR4-induced inflammatory lung injury seen in Cd38 /  mice.	ibrutinib	141-150	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	127-130
34994565-5	2022	The fluorobenzene (FB) solvate of Bruton"s tyrosine kinase inhibitor Ibrutinib (IBR) was used as a model system.	ibrutinib	69-78	Bruton tyrosine kinase	Homo sapiens	34-58
34706199-10	2022	Cd38 /  macrophages displayed markedly increased activation of Btk, NF-KappaB, and NLRP3 whereas in vivo administration of the Btk inhibitor ibrutinib (a FDA approved drug) prevented augmented TLR4-induced inflammatory lung injury seen in Cd38 /  mice.	ibrutinib	141-150	toll-like receptor 4	Mus musculus	193-197
34994565-5	2022	The fluorobenzene (FB) solvate of Bruton"s tyrosine kinase inhibitor Ibrutinib (IBR) was used as a model system.	ibrutinib	80-83	Bruton tyrosine kinase	Homo sapiens	34-58
35076567-6	2022	Several studies have recently shown that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has promising results in the treatment of R/R PCNSL.	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	54-76
35096069-2	2022	Ibrutinib, acalabrutinib, and zanubrutinib are Bruton tyrosine kinase (BTK) inhibitors approved for certain indolent B cell non-Hodgkin"s lymphoma (NHL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	47-69
35096069-2	2022	Ibrutinib, acalabrutinib, and zanubrutinib are Bruton tyrosine kinase (BTK) inhibitors approved for certain indolent B cell non-Hodgkin"s lymphoma (NHL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	71-74
35047578-1	2021	Introduction: Ibrutinib, a Bruton"s tyrosine kinase inhibitor (TKI) used primarily in the treatment of hematologic malignancies, has been associated with increased incidence of atrial fibrillation (AF), with limited data on its association with other tachyarrhythmias.	ibrutinib	14-23	Bruton tyrosine kinase	Homo sapiens	27-51
34758069-7	2022	Ibrutinib-associated risk for bleeding (33.5%) was decreased by prohibiting use of oral anticoagulants through an amendment of the study protocol and by avoiding CYP3A4 drug-drug interactions.	ibrutinib	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	162-168
35123927-4	2022	The Bruton"s tyrosine kinase (BTK) inhibitors, including ibrutinib, acalabrutinib, and zanubrutinib, are highly active in MCL and currently approved for treating patients with relapsed disease.	ibrutinib	57-66	Bruton tyrosine kinase	Homo sapiens	4-28
35123927-4	2022	The Bruton"s tyrosine kinase (BTK) inhibitors, including ibrutinib, acalabrutinib, and zanubrutinib, are highly active in MCL and currently approved for treating patients with relapsed disease.	ibrutinib	57-66	Bruton tyrosine kinase	Homo sapiens	30-33
35053255-0	2022	The Mucolipin TRPML2 Channel Enhances the Sensitivity of Multiple Myeloma Cell Lines to Ibrutinib and/or Bortezomib Treatment.	ibrutinib	88-97	mucolipin TRP cation channel 2	Homo sapiens	14-20
35053255-3	2022	In addition, the relationship between the expression of TRPML2 channels and chemosensitivity of different MM cell lines to Ibrutinib administered alone or in combination with Bortezomib has been evaluated.	ibrutinib	123-132	mucolipin TRP cation channel 2	Homo sapiens	56-62
35053255-4	2022	By RT-PCR and Western blot analysis, we found that the Ibrutinib-resistant U266 cells showed lower TRPML2 expression, whereas higher TRPML2 mRNA and protein levels were evidenced in RPMI cells.	ibrutinib	55-64	mucolipin TRP cation channel 2	Homo sapiens	99-105
35053255-4	2022	By RT-PCR and Western blot analysis, we found that the Ibrutinib-resistant U266 cells showed lower TRPML2 expression, whereas higher TRPML2 mRNA and protein levels were evidenced in RPMI cells.	ibrutinib	55-64	mucolipin TRP cation channel 2	Homo sapiens	133-139
35053255-5	2022	Moreover, TRPML2 gene silencing in RPMI cells markedly reverted the effects induced by Ibrutinib alone or in combination with Bortezomib suggesting that the sensitivity to Ibrutinib is TRPML2 mediated.	ibrutinib	87-96	mucolipin TRP cation channel 2	Homo sapiens	10-16
35053255-5	2022	Moreover, TRPML2 gene silencing in RPMI cells markedly reverted the effects induced by Ibrutinib alone or in combination with Bortezomib suggesting that the sensitivity to Ibrutinib is TRPML2 mediated.	ibrutinib	87-96	mucolipin TRP cation channel 2	Homo sapiens	185-191
35053255-5	2022	Moreover, TRPML2 gene silencing in RPMI cells markedly reverted the effects induced by Ibrutinib alone or in combination with Bortezomib suggesting that the sensitivity to Ibrutinib is TRPML2 mediated.	ibrutinib	172-181	mucolipin TRP cation channel 2	Homo sapiens	10-16
35053255-5	2022	Moreover, TRPML2 gene silencing in RPMI cells markedly reverted the effects induced by Ibrutinib alone or in combination with Bortezomib suggesting that the sensitivity to Ibrutinib is TRPML2 mediated.	ibrutinib	172-181	mucolipin TRP cation channel 2	Homo sapiens	185-191
35053255-6	2022	In conclusion, this study suggests that the expression of TRPML2 in MM cells increases the sensitivity to Ibrutinib treatment, suggesting for a potential stratification of Ibrutinib sensitivity of MM patients on the basis of the TRPML2 expression.	ibrutinib	106-115	mucolipin TRP cation channel 2	Homo sapiens	58-64
35053255-6	2022	In conclusion, this study suggests that the expression of TRPML2 in MM cells increases the sensitivity to Ibrutinib treatment, suggesting for a potential stratification of Ibrutinib sensitivity of MM patients on the basis of the TRPML2 expression.	ibrutinib	172-181	mucolipin TRP cation channel 2	Homo sapiens	58-64
35076567-6	2022	Several studies have recently shown that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has promising results in the treatment of R/R PCNSL.	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	78-81
35115740-2	2022	Few clinical studies have reported the use of Ibrutinib, a covalent Bruton Tyrosine kinase (BTK) inhibitor, in RR DLBCL.	ibrutinib	46-55	Bruton tyrosine kinase	Homo sapiens	68-90
35115740-2	2022	Few clinical studies have reported the use of Ibrutinib, a covalent Bruton Tyrosine kinase (BTK) inhibitor, in RR DLBCL.	ibrutinib	46-55	Bruton tyrosine kinase	Homo sapiens	92-95
35008919-7	2022	In contrast, the Btk inhibitor, ibrutinib, causes only a minor decrease in thrombus contractile score.	ibrutinib	32-41	Bruton tyrosine kinase	Homo sapiens	17-20
34975325-0	2022	Conjugate of ibrutinib with a TLR7 agonist suppresses melanoma progression and enhances antitumor immunity.	ibrutinib	13-22	toll-like receptor 7	Mus musculus	30-34
34975325-5	2022	GY161, as a representative ImmunTac, was synthesized via chemical conjugation of ibrutinib with a TLR7 agonist.	ibrutinib	81-90	toll-like receptor 7	Mus musculus	98-102
33831782-4	2021	Mice were injected for 4 weeks with the NLRP3 inhibitor MCC950, the BTK inhibitor ibrutinib or vehicle control.	ibrutinib	82-91	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	68-71
35169086-5	2022	The first-generation BTK inhibitor ibrutinib has been widely studied in clinical trials for PCNSL and systemic non-GCB DLBCL.	ibrutinib	35-44	Bruton tyrosine kinase	Homo sapiens	21-24
34987640-9	2022	Further, to reactivate functionally indolent TILs, we reprogrammed ex vivo TILs with Ibrutinib plus Rapamycin to block interleukin-2-inducible kinase (ITK) and mTOR pathways, respectively.	ibrutinib	85-94	IL2 inducible T cell kinase	Homo sapiens	119-149
34987640-9	2022	Further, to reactivate functionally indolent TILs, we reprogrammed ex vivo TILs with Ibrutinib plus Rapamycin to block interleukin-2-inducible kinase (ITK) and mTOR pathways, respectively.	ibrutinib	85-94	IL2 inducible T cell kinase	Homo sapiens	151-154
34987640-9	2022	Further, to reactivate functionally indolent TILs, we reprogrammed ex vivo TILs with Ibrutinib plus Rapamycin to block interleukin-2-inducible kinase (ITK) and mTOR pathways, respectively.	ibrutinib	85-94	mechanistic target of rapamycin kinase	Homo sapiens	160-164
33900450-3	2021	This study aimed to investigate the efficacy and safety of ibrutinib plus BCL2 inhibitor venetoclax in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression.	ibrutinib	59-68	BCL2 apoptosis regulator	Homo sapiens	147-151
33900450-14	2021	Combined therapy of ibrutinib and venetoclax showed promising efficacy and synergistic effects in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression, and the toxicities were well-tolerated.	ibrutinib	20-29	BCL2 apoptosis regulator	Homo sapiens	142-146
34031271-2	2021	Ibrutinib is a bruton"s tyrosine kinase inhibitor in innate immune cells such as the neutrophils that diminishes their activation and influx to the site of injury.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	15-39
34028865-0	2021	A case of Chronic Lymphocytic Leukemia-associated insect bite-like reaction responding to Ibrutinib, an immunomodulatory Bruton"s Tyrosine Kinase inhibito.	ibrutinib	90-99	Bruton tyrosine kinase	Homo sapiens	121-145
34046681-6	2021	In addition to BTK, ibrutinib also inhibits IL2 inducible T cell Kinase (ITK).	ibrutinib	20-29	IL2 inducible T cell kinase	Homo sapiens	44-71
34046681-6	2021	In addition to BTK, ibrutinib also inhibits IL2 inducible T cell Kinase (ITK).	ibrutinib	20-29	IL2 inducible T cell kinase	Homo sapiens	73-76
34019713-1	2021	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has revolutionised the therapeutic landscape of chronic lymphocytic leukaemia (CLL).	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
34019713-1	2021	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has revolutionised the therapeutic landscape of chronic lymphocytic leukaemia (CLL).	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
34019713-2	2021	Acquired mutations emerging at position C481 in the BTK tyrosine kinase domain are the predominant genetic alterations associated with secondary ibrutinib resistance.	ibrutinib	145-154	Bruton tyrosine kinase	Homo sapiens	52-55
34019713-6	2021	Subsequent Bcl-2 inhibition therapy applied in 28/32 patients harbouring BTKC481S and progressing on ibrutinib conferred clinical and molecular remission across the patients.	ibrutinib	101-110	BCL2 apoptosis regulator	Homo sapiens	11-16
34018029-11	2021	Among patients with IRRs, those receiving ibrutinib-obinutuzumab had lower post-obinutuzumab increases in IL-6, IL-8, IL-10, and MCP-1 (P < 0.04) than patients receiving chlorambucil-obinutuzumab.	ibrutinib	42-51	interleukin 6	Homo sapiens	106-110
34038714-0	2021	Comparison of the drug-drug interactions potential of ibrutinib and acalabrutinib via inhibition of UDP-glucuronosyltransferase.	ibrutinib	54-63	UDP glucuronosyltransferase family 1 member A complex locus	Homo sapiens	100-127
34038714-1	2021	Ibrutinib and acalabrutinib are two Bruton"s tyrosine kinase (BTK) inhibitors which have gained Food and Drug Administration (FDA) approval for the treatment of various B cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	36-60
34038714-1	2021	Ibrutinib and acalabrutinib are two Bruton"s tyrosine kinase (BTK) inhibitors which have gained Food and Drug Administration (FDA) approval for the treatment of various B cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	62-65
34018029-11	2021	Among patients with IRRs, those receiving ibrutinib-obinutuzumab had lower post-obinutuzumab increases in IL-6, IL-8, IL-10, and MCP-1 (P < 0.04) than patients receiving chlorambucil-obinutuzumab.	ibrutinib	42-51	C-X-C motif chemokine ligand 8	Homo sapiens	112-116
34038714-3	2021	Our data indicated that ibrutinib exerted broad inhibition on most of UGTs, including a potent competitive inhibition against UGT1A1 with a Ki value of 0.90 +- 0.03 muM, a noncompetitive inhibition against UGT1A3 and UGT1A7 with Ki values of 0.88 +- 0.03 muM and 2.52 +- 0.23 muM, respectively, while acalabrutinib only exhibited weak UGT inhibition towards all tested UGT isoforms.	ibrutinib	24-33	UDP glucuronosyltransferase family 1 member A1	Homo sapiens	126-132
34038714-3	2021	Our data indicated that ibrutinib exerted broad inhibition on most of UGTs, including a potent competitive inhibition against UGT1A1 with a Ki value of 0.90 +- 0.03 muM, a noncompetitive inhibition against UGT1A3 and UGT1A7 with Ki values of 0.88 +- 0.03 muM and 2.52 +- 0.23 muM, respectively, while acalabrutinib only exhibited weak UGT inhibition towards all tested UGT isoforms.	ibrutinib	24-33	UDP glucuronosyltransferase family 1 member A3	Homo sapiens	206-212
34038714-3	2021	Our data indicated that ibrutinib exerted broad inhibition on most of UGTs, including a potent competitive inhibition against UGT1A1 with a Ki value of 0.90 +- 0.03 muM, a noncompetitive inhibition against UGT1A3 and UGT1A7 with Ki values of 0.88 +- 0.03 muM and 2.52 +- 0.23 muM, respectively, while acalabrutinib only exhibited weak UGT inhibition towards all tested UGT isoforms.	ibrutinib	24-33	UDP glucuronosyltransferase family 1 member A7	Homo sapiens	217-223
34038714-3	2021	Our data indicated that ibrutinib exerted broad inhibition on most of UGTs, including a potent competitive inhibition against UGT1A1 with a Ki value of 0.90 +- 0.03 muM, a noncompetitive inhibition against UGT1A3 and UGT1A7 with Ki values of 0.88 +- 0.03 muM and 2.52 +- 0.23 muM, respectively, while acalabrutinib only exhibited weak UGT inhibition towards all tested UGT isoforms.	ibrutinib	24-33	UDP glucuronosyltransferase family 1 member A complex locus	Homo sapiens	70-73
34038714-3	2021	Our data indicated that ibrutinib exerted broad inhibition on most of UGTs, including a potent competitive inhibition against UGT1A1 with a Ki value of 0.90 +- 0.03 muM, a noncompetitive inhibition against UGT1A3 and UGT1A7 with Ki values of 0.88 +- 0.03 muM and 2.52 +- 0.23 muM, respectively, while acalabrutinib only exhibited weak UGT inhibition towards all tested UGT isoforms.	ibrutinib	24-33	UDP glucuronosyltransferase family 1 member A complex locus	Homo sapiens	126-129
34038714-4	2021	DDI risk prediction suggested that the inhibition against UGT1A1 and UGT1A3 by ibrutinib might bring a potential DDIs risk, while acalabrutinib was unlikely to trigger clinically significant UGT-mediated DDIs due to its weak effects.	ibrutinib	79-88	UDP glucuronosyltransferase family 1 member A1	Homo sapiens	58-64
34038714-4	2021	DDI risk prediction suggested that the inhibition against UGT1A1 and UGT1A3 by ibrutinib might bring a potential DDIs risk, while acalabrutinib was unlikely to trigger clinically significant UGT-mediated DDIs due to its weak effects.	ibrutinib	79-88	UDP glucuronosyltransferase family 1 member A3	Homo sapiens	69-75
34038714-4	2021	DDI risk prediction suggested that the inhibition against UGT1A1 and UGT1A3 by ibrutinib might bring a potential DDIs risk, while acalabrutinib was unlikely to trigger clinically significant UGT-mediated DDIs due to its weak effects.	ibrutinib	79-88	UDP glucuronosyltransferase family 1 member A complex locus	Homo sapiens	58-61
34018029-11	2021	Among patients with IRRs, those receiving ibrutinib-obinutuzumab had lower post-obinutuzumab increases in IL-6, IL-8, IL-10, and MCP-1 (P < 0.04) than patients receiving chlorambucil-obinutuzumab.	ibrutinib	42-51	interleukin 10	Homo sapiens	118-123
34018029-11	2021	Among patients with IRRs, those receiving ibrutinib-obinutuzumab had lower post-obinutuzumab increases in IL-6, IL-8, IL-10, and MCP-1 (P < 0.04) than patients receiving chlorambucil-obinutuzumab.	ibrutinib	42-51	C-C motif chemokine ligand 2	Homo sapiens	129-134
34018029-12	2021	For patients in the ibrutinib-treatment arm, we observed a reduction in both the rate of clinically apparent IRRs and the levels of IRR-related cytokines and chemokines.	ibrutinib	20-29	insulin receptor related receptor	Homo sapiens	109-112
34040961-4	2021	Both patients were treated with single agent ibrutinib, a Bruton"s tyrosine kinase inhibitor (BTKi), and achieved rapid, deep and durable responses.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	58-82
34040961-4	2021	Both patients were treated with single agent ibrutinib, a Bruton"s tyrosine kinase inhibitor (BTKi), and achieved rapid, deep and durable responses.	ibrutinib	45-54	inhibitor of Bruton tyrosine kinase	Homo sapiens	94-98
33963002-0	2021	Clinical Outcomes in Patients with Multi-Hit TP53 Chronic Lymphocytic Leukemia Treated with Ibrutinib.	ibrutinib	92-101	tumor protein p53	Homo sapiens	45-49
34040960-4	2021	We herein, report an unusual presentation of a Lebanese CLL patient with two cytogenetic abnormalities: trisomy 12 and t(14;18)(q32;q21), along with an unmutated IGHV, displaying a favorable response to ibrutinib with a maintained complete remission.	ibrutinib	203-212	immunoglobulin heavy variable 3-69-1 (pseudogene)	Homo sapiens	162-166
34000704-1	2021	Ibrutinib, a potent irreversible Bruton"s tyrosine kinase (BTK) inhibitor, was approved by the FDA for treating mantle cell lymphoma (MCL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	33-57
34000704-1	2021	Ibrutinib, a potent irreversible Bruton"s tyrosine kinase (BTK) inhibitor, was approved by the FDA for treating mantle cell lymphoma (MCL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	59-62
34000704-2	2021	Although ibrutinib exhibited excellent antitumor activity, it was associated with certain adverse reactions, with off-target effects against EGFR, Itk and Src family kinases.	ibrutinib	9-18	epidermal growth factor receptor	Homo sapiens	141-145
34000704-2	2021	Although ibrutinib exhibited excellent antitumor activity, it was associated with certain adverse reactions, with off-target effects against EGFR, Itk and Src family kinases.	ibrutinib	9-18	IL2 inducible T cell kinase	Homo sapiens	147-150
33963002-10	2021	Conclusions: In this study, single-hit TP53 defines a distinct subgroup of patients with an excellent long-term response to single-agent ibrutinib, while multi-hit TP53 is independently associated with shorter PFS.	ibrutinib	137-146	tumor protein p53	Homo sapiens	39-43
33524816-9	2021	Among them, the limit of detection (LOD) and limit of quantification (LOQ) of ibrutinib and pralatrexate were in the range of 0.11-0.76 ng mL-1 and 0.21-1.12 ng mL-1, respectively, which were lower than the corresponding blood concentrations.	ibrutinib	78-87	L1 cell adhesion molecule	Mus musculus	139-143
33171493-8	2021	This regulatory loop is disrupted by "BCR inhibitors" (BTK inhibitor ibrutinib or PI3K inhibitor idelalisib).	ibrutinib	69-78	Bruton tyrosine kinase	Homo sapiens	55-58
33740548-2	2021	The first generation of BTK inhibitor, Ibrutinib, achieved remarkable progress in the treatment of B-cell malignancies, but still has problems with drug-resistance or off-target induced serious side effects.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	24-27
33524816-9	2021	Among them, the limit of detection (LOD) and limit of quantification (LOQ) of ibrutinib and pralatrexate were in the range of 0.11-0.76 ng mL-1 and 0.21-1.12 ng mL-1, respectively, which were lower than the corresponding blood concentrations.	ibrutinib	78-87	L1 cell adhesion molecule	Mus musculus	161-165
32855532-3	2021	Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib provides a potential therapeutic approach for the DLBCL but fails to improve the outcome in the phase III trial.	ibrutinib	41-50	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	0-24
32855532-3	2021	Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib provides a potential therapeutic approach for the DLBCL but fails to improve the outcome in the phase III trial.	ibrutinib	41-50	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	26-29
33539945-2	2021	Ibrutinib, a Bruton"s tyrosine kinase inhibitor, exhibits antitumor activity through tumor microenvironment modulation.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-37
33828254-2	2021	Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy.	ibrutinib	25-34	spermatogenesis associated 2	Homo sapiens	80-84
33760219-8	2021	BTK inhibitors [ibrutinib (10 microM), CNX-774 (10 microM)] significantly attenuated TPA-induced cell invasion and migration in MCF-7 cells and inhibited the activation of the phospholipase Cgamma2/PKCbeta signaling pathways.	ibrutinib	16-25	Bruton tyrosine kinase	Homo sapiens	0-3
33561536-9	2021	In addition, with the application of ibrutinib, the selective inhibitor of BTK, it was proclaimed that the administration of GEN restrained the activation of JAK2/STAT1 pathway via attenuating the hyperphosphorylation of BTK both in mice and BV2 cells.	ibrutinib	37-46	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	75-78
33561536-9	2021	In addition, with the application of ibrutinib, the selective inhibitor of BTK, it was proclaimed that the administration of GEN restrained the activation of JAK2/STAT1 pathway via attenuating the hyperphosphorylation of BTK both in mice and BV2 cells.	ibrutinib	37-46	Janus kinase 2	Mus musculus	158-162
33561536-9	2021	In addition, with the application of ibrutinib, the selective inhibitor of BTK, it was proclaimed that the administration of GEN restrained the activation of JAK2/STAT1 pathway via attenuating the hyperphosphorylation of BTK both in mice and BV2 cells.	ibrutinib	37-46	signal transducer and activator of transcription 1	Mus musculus	163-168
33561536-9	2021	In addition, with the application of ibrutinib, the selective inhibitor of BTK, it was proclaimed that the administration of GEN restrained the activation of JAK2/STAT1 pathway via attenuating the hyperphosphorylation of BTK both in mice and BV2 cells.	ibrutinib	37-46	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	221-224
33932067-0	2021	Ibrutinib improves the efficacy of anti-CD19-CAR T-cell therapy in patients with refractory non-Hodgkin lymphoma.	ibrutinib	0-9	CD19 molecule	Homo sapiens	40-44
33932067-0	2021	Ibrutinib improves the efficacy of anti-CD19-CAR T-cell therapy in patients with refractory non-Hodgkin lymphoma.	ibrutinib	0-9	CXADR pseudogene 1	Homo sapiens	45-48
33932067-8	2021	The successful outcome of the second-time anti-CD19-CAR T-cell therapy might suggest that the previous ibrutinib treatment improved the activities of anti-CD19-CAR T cells.	ibrutinib	103-112	CD19 molecule	Homo sapiens	47-51
33932067-8	2021	The successful outcome of the second-time anti-CD19-CAR T-cell therapy might suggest that the previous ibrutinib treatment improved the activities of anti-CD19-CAR T cells.	ibrutinib	103-112	CXADR pseudogene 1	Homo sapiens	52-55
33932067-8	2021	The successful outcome of the second-time anti-CD19-CAR T-cell therapy might suggest that the previous ibrutinib treatment improved the activities of anti-CD19-CAR T cells.	ibrutinib	103-112	CD19 molecule	Homo sapiens	155-159
33932067-8	2021	The successful outcome of the second-time anti-CD19-CAR T-cell therapy might suggest that the previous ibrutinib treatment improved the activities of anti-CD19-CAR T cells.	ibrutinib	103-112	CXADR pseudogene 1	Homo sapiens	160-163
33740218-1	2021	BACKGROUND AND OBJECTIVES: Ibrutinib is an antineoplastic agent that reduces B-cell proliferation by inhibiting Bruton"s tyrosine kinase.	ibrutinib	27-36	Bruton tyrosine kinase	Homo sapiens	112-136
33760219-8	2021	BTK inhibitors [ibrutinib (10 microM), CNX-774 (10 microM)] significantly attenuated TPA-induced cell invasion and migration in MCF-7 cells and inhibited the activation of the phospholipase Cgamma2/PKCbeta signaling pathways.	ibrutinib	16-25	phospholipase C gamma 2	Homo sapiens	176-197
33760219-8	2021	BTK inhibitors [ibrutinib (10 microM), CNX-774 (10 microM)] significantly attenuated TPA-induced cell invasion and migration in MCF-7 cells and inhibited the activation of the phospholipase Cgamma2/PKCbeta signaling pathways.	ibrutinib	16-25	protein kinase C alpha	Homo sapiens	198-205
33912812-1	2021	Ibrutinib is a covalently binding inhibitor of the B-cell receptor signaling-mediator Bruton"s tyrosine kinase (BTK) with great efficacy in chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	86-110
33946867-0	2021	Integration of Metabolomics and Gene Expression Profiling Elucidates IL4I1 as Modulator of Ibrutinib Resistance in ABC-Diffuse Large B Cell Lymphoma.	ibrutinib	91-100	interleukin 4 induced 1	Homo sapiens	69-74
33946867-0	2021	Integration of Metabolomics and Gene Expression Profiling Elucidates IL4I1 as Modulator of Ibrutinib Resistance in ABC-Diffuse Large B Cell Lymphoma.	ibrutinib	91-100	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	115-118
33946867-5	2021	In this study, we explored for the first time the metabolic regulators of ibrutinib-resistant activated B-cell (ABC) DLBCL using a multi-omics analysis that integrated metabolomics (using high-resolution mass spectrometry) and transcriptomic (gene expression analysis).	ibrutinib	74-83	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	112-115
33946867-9	2021	Our report shows how these cells become dependent on PI3K/AKT signaling for survival after acquiring ibrutinib resistance and shift to sustained oxidative phosphorylation; additionally, we outline the compensatory pathway that might regulate this metabolic reprogramming in the drug-resistant cells.	ibrutinib	101-110	AKT serine/threonine kinase 1	Homo sapiens	58-61
33912812-1	2021	Ibrutinib is a covalently binding inhibitor of the B-cell receptor signaling-mediator Bruton"s tyrosine kinase (BTK) with great efficacy in chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	112-115
33893887-4	2021	Positron emission tomography (PET) can be a useful diagnostic tool, and case reports suggest that the Bruton"s tyrosine kinase inhibitor ibrutinib may have therapeutic potential.	ibrutinib	137-146	Bruton tyrosine kinase	Homo sapiens	102-126
33856277-2	2021	Ibrutinib and lenalidomide are synergistic in vitro in ABC DLBCL and may augment salvage chemotherapy.	ibrutinib	0-9	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	55-58
33875521-0	2021	Select antitumor cytotoxic CD8+ T clonotypes expand in patients with chronic lymphocytic leukemia treated with ibrutinib.	ibrutinib	111-120	CD8a molecule	Homo sapiens	27-30
33875521-2	2021	Ibrutinib, a standard treatment for CLL, inhibits not only Bruton tyrosine kinase of the B-cell receptor signaling pathway, but also interleukin-2-inducible kinase of the TCR signaling pathway.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	59-81
33419778-8	2021	The shRNA-mediated knock-down of BTK expression in primary human non-malignant lymph node-derived B cells resulted in strong anti-IG-induced AKT activation, as did the degradation of BTK protein in cells lines using ibrutinib-based proteolysis targeting chimera (PROTAC).	ibrutinib	216-225	Bruton tyrosine kinase	Homo sapiens	33-36
33419778-8	2021	The shRNA-mediated knock-down of BTK expression in primary human non-malignant lymph node-derived B cells resulted in strong anti-IG-induced AKT activation, as did the degradation of BTK protein in cells lines using ibrutinib-based proteolysis targeting chimera (PROTAC).	ibrutinib	216-225	Bruton tyrosine kinase	Homo sapiens	183-186
33937038-0	2021	TH2/TH1 Shift Under Ibrutinib Treatment in Chronic Lymphocytic Leukemia.	ibrutinib	20-29	negative elongation factor complex member C/D	Homo sapiens	4-7
33937038-1	2021	Ibrutinib may revert the T-helper (Th)2 polarization observed in chronic lymphocytic leukemia (CLL) by targeting the IL-2-inducible kinase, that shows a significant homology with the Bruton tyrosine kinase.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	183-205
33937038-7	2021	Ibrutinib may shape the CLL T-cell profile, limiting Th2 activation and inducing a shift in the Th2/Th1 ratio.	ibrutinib	0-9	negative elongation factor complex member C/D	Homo sapiens	100-103
33937038-8	2021	The association between the Th2/Th1 ratio decrease and the CR achievement suggests the in vivo generation of a potential host anti-tumor immune activation induced by ibrutinib.	ibrutinib	166-175	negative elongation factor complex member C/D	Homo sapiens	32-35
33851389-4	2021	Here we propose inhibitors of Bruton tyrosine kinase (Btk) approved for B-cell malignancies (e.g. ibrutinib) as another therapeutic option in VIPIT, as they are expected to pleiotropically target multiple pathways downstream of FcgammaRIIA-mediated Btk activation, e.g. as demonstrated for the effective inhibition of platelet aggregation, dense granule secretion, P-selectin expression and platelet-neutrophil aggregate formation stimulated by FcgammaRIIA cross-linking.	ibrutinib	98-107	Bruton tyrosine kinase	Homo sapiens	30-52
33851389-4	2021	Here we propose inhibitors of Bruton tyrosine kinase (Btk) approved for B-cell malignancies (e.g. ibrutinib) as another therapeutic option in VIPIT, as they are expected to pleiotropically target multiple pathways downstream of FcgammaRIIA-mediated Btk activation, e.g. as demonstrated for the effective inhibition of platelet aggregation, dense granule secretion, P-selectin expression and platelet-neutrophil aggregate formation stimulated by FcgammaRIIA cross-linking.	ibrutinib	98-107	Bruton tyrosine kinase	Homo sapiens	54-57
33981831-1	2021	Bruton tyrosine kinase (BTK) inhibitor ibrutinib has been validated as an effective drug to treat B cell malignancies.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	0-22
33981831-1	2021	Bruton tyrosine kinase (BTK) inhibitor ibrutinib has been validated as an effective drug to treat B cell malignancies.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	24-27
33981831-3	2021	However, the off-target inhibition of ibrutinib on interleukin-2 (IL-2)-inducible T cell kinase (ITK) may reduce rituximab"s antibody-dependent cellular cytotoxicity (ADCC) efficacy.	ibrutinib	38-47	interleukin 2	Homo sapiens	51-64
33981831-3	2021	However, the off-target inhibition of ibrutinib on interleukin-2 (IL-2)-inducible T cell kinase (ITK) may reduce rituximab"s antibody-dependent cellular cytotoxicity (ADCC) efficacy.	ibrutinib	38-47	IL2 inducible T cell kinase	Homo sapiens	66-95
33981831-3	2021	However, the off-target inhibition of ibrutinib on interleukin-2 (IL-2)-inducible T cell kinase (ITK) may reduce rituximab"s antibody-dependent cellular cytotoxicity (ADCC) efficacy.	ibrutinib	38-47	IL2 inducible T cell kinase	Homo sapiens	97-100
33851691-3	2021	Ibrutinib, a first-in-class BTK inhibitor, has been approved for the treatment of several types of B-cell malignancies worldwide.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	28-31
33216986-2	2021	Ibrutinib is a first-in-class Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of patients with CLL/SLL or relapsed/refractory MCL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	30-52
33216986-2	2021	Ibrutinib is a first-in-class Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of patients with CLL/SLL or relapsed/refractory MCL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	54-57
33216986-2	2021	Ibrutinib is a first-in-class Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of patients with CLL/SLL or relapsed/refractory MCL.	ibrutinib	0-9	solute carrier family 35 member B2	Homo sapiens	114-121
33216986-3	2021	However, next-generation BTK inhibitors have been developed with improved specificity and the potential to reduce the off-target toxicity observed with ibrutinib.	ibrutinib	152-161	Bruton tyrosine kinase	Homo sapiens	25-28
33593794-8	2021	We investigated the impact of modulating ITK signaling with ibrutinib, an FDA-approved tyrosine kinase inhibitor, and found that anti-OX40/anti-CTLA-4/ibrutinib therapy further enhanced CD8+ T cell-specific Eomes expression, leading to enhanced tumor regression and improved survival, both of which were associated with increased T-cell effector function across multiple tumor models.	ibrutinib	60-69	IL2 inducible T cell kinase	Homo sapiens	41-44
33593794-8	2021	We investigated the impact of modulating ITK signaling with ibrutinib, an FDA-approved tyrosine kinase inhibitor, and found that anti-OX40/anti-CTLA-4/ibrutinib therapy further enhanced CD8+ T cell-specific Eomes expression, leading to enhanced tumor regression and improved survival, both of which were associated with increased T-cell effector function across multiple tumor models.	ibrutinib	60-69	TNF receptor superfamily member 4	Homo sapiens	134-138
33593794-8	2021	We investigated the impact of modulating ITK signaling with ibrutinib, an FDA-approved tyrosine kinase inhibitor, and found that anti-OX40/anti-CTLA-4/ibrutinib therapy further enhanced CD8+ T cell-specific Eomes expression, leading to enhanced tumor regression and improved survival, both of which were associated with increased T-cell effector function across multiple tumor models.	ibrutinib	60-69	cytotoxic T-lymphocyte associated protein 4	Homo sapiens	144-150
33593794-8	2021	We investigated the impact of modulating ITK signaling with ibrutinib, an FDA-approved tyrosine kinase inhibitor, and found that anti-OX40/anti-CTLA-4/ibrutinib therapy further enhanced CD8+ T cell-specific Eomes expression, leading to enhanced tumor regression and improved survival, both of which were associated with increased T-cell effector function across multiple tumor models.	ibrutinib	60-69	CD8a molecule	Homo sapiens	186-189
33593794-8	2021	We investigated the impact of modulating ITK signaling with ibrutinib, an FDA-approved tyrosine kinase inhibitor, and found that anti-OX40/anti-CTLA-4/ibrutinib therapy further enhanced CD8+ T cell-specific Eomes expression, leading to enhanced tumor regression and improved survival, both of which were associated with increased T-cell effector function across multiple tumor models.	ibrutinib	151-160	IL2 inducible T cell kinase	Homo sapiens	41-44
33593794-8	2021	We investigated the impact of modulating ITK signaling with ibrutinib, an FDA-approved tyrosine kinase inhibitor, and found that anti-OX40/anti-CTLA-4/ibrutinib therapy further enhanced CD8+ T cell-specific Eomes expression, leading to enhanced tumor regression and improved survival, both of which were associated with increased T-cell effector function across multiple tumor models.	ibrutinib	151-160	CD8a molecule	Homo sapiens	186-189
33593794-8	2021	We investigated the impact of modulating ITK signaling with ibrutinib, an FDA-approved tyrosine kinase inhibitor, and found that anti-OX40/anti-CTLA-4/ibrutinib therapy further enhanced CD8+ T cell-specific Eomes expression, leading to enhanced tumor regression and improved survival, both of which were associated with increased T-cell effector function across multiple tumor models.	ibrutinib	151-160	eomesodermin	Homo sapiens	207-212
33851691-4	2021	However, ibrutinib has off-target activities on non-BTK kinase that are related to adverse effects or might translate into clinical limitations.	ibrutinib	9-18	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	52-55
32139435-0	2021	Combining ibrutinib and checkpoint blockade improves CD8+ T-cell function and control of chronic lymphocytic leukemia in Em-TCL1 mice.	ibrutinib	10-19	T cell lymphoma breakpoint 1	Mus musculus	124-128
32139435-1	2021	Ibrutinib is a bruton"s tyrosine kinase (BTK) inhibitor approved for the treatment of multiple B-cell malignancies, including chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	15-39
32139435-1	2021	Ibrutinib is a bruton"s tyrosine kinase (BTK) inhibitor approved for the treatment of multiple B-cell malignancies, including chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	41-44
32139435-2	2021	In addition to blocking B-cell receptor signaling and chemokine receptor-mediated pathways in CLL cells, that are known drivers of disease, ibrutinib also affects the microenvironment in CLL via targeting BTK in myeloid cells and IL-2-inducible T-cell kinase (ITK) in T-cells.	ibrutinib	140-149	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	205-208
32139435-2	2021	In addition to blocking B-cell receptor signaling and chemokine receptor-mediated pathways in CLL cells, that are known drivers of disease, ibrutinib also affects the microenvironment in CLL via targeting BTK in myeloid cells and IL-2-inducible T-cell kinase (ITK) in T-cells.	ibrutinib	140-149	IL2 inducible T cell kinase	Mus musculus	230-258
32139435-2	2021	In addition to blocking B-cell receptor signaling and chemokine receptor-mediated pathways in CLL cells, that are known drivers of disease, ibrutinib also affects the microenvironment in CLL via targeting BTK in myeloid cells and IL-2-inducible T-cell kinase (ITK) in T-cells.	ibrutinib	140-149	IL2 inducible T cell kinase	Mus musculus	260-263
32139435-3	2021	These non-BTK effects were suggested to contribute to the success of ibrutinib in CLL.	ibrutinib	69-78	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	10-13
32139435-4	2021	By using the Emicro-TCL1 adoptive transfer mouse model of CLL, we observed that ibrutinib effectively controls leukemia development, but also results in significantly lower numbers of CD8+ effector T-cells, with lower expression of activation markers, as well as impaired proliferation and effector function.	ibrutinib	80-89	T cell lymphoma breakpoint 1	Mus musculus	20-24
32139435-6	2021	Most interestingly, combination of ibrutinib with blocking antibodies targeting PD-1/PD-L1 axis in vivo improved CD8+ T-cell effector function and control of CLL.	ibrutinib	35-44	CD274 antigen	Mus musculus	85-90
32381576-7	2021	In addition, DC1-192 showed synergy with bortezomib and ibrutinib; synergy with ibrutinib was enhanced when CLL cells were co-cultured on CD40L-expressing fibroblasts in order to mimic the cytoprotective lymph node microenvironment (P = 0.01).	ibrutinib	80-89	CD40 ligand	Homo sapiens	138-143
32381576-8	2021	Given that NF-kappaB plays a role in both bortezomib and ibrutinib resistance mechanisms, these data provide a strong rationale for the use of DC-1-192 in the treatment of NF-kappaB-driven cancers, particularly in the context of relapsed/refractory disease.	ibrutinib	57-66	nuclear factor kappa B subunit 1	Homo sapiens	11-20
32728184-7	2021	Finally, we showed that ADAR knockout decreased steady state viability of MEC1 cells and made them more susceptible to treatment with fludarabine and ibrutinib in vitro.	ibrutinib	150-159	adenosine deaminase, RNA-specific	Mus musculus	24-28
33222046-2	2021	Although no standard treatment has yet been established, patients with BNS harboring the MYD88 L265P mutation have been reported to respond favorably to ibrutinib, which can cross the blood-brain barrier and trigger apoptosis of MYD88 L265P-positive LPCs.	ibrutinib	153-162	MYD88 innate immune signal transduction adaptor	Homo sapiens	89-94
33222046-2	2021	Although no standard treatment has yet been established, patients with BNS harboring the MYD88 L265P mutation have been reported to respond favorably to ibrutinib, which can cross the blood-brain barrier and trigger apoptosis of MYD88 L265P-positive LPCs.	ibrutinib	153-162	MYD88 innate immune signal transduction adaptor	Homo sapiens	229-234
33222046-4	2021	Here, we report the case of a patient with BNS receiving ibrutinib in whom we detected relapse early by monitoring for molecular residual disease (MRD) based on the presence of the MYD88 L265P mutation in cerebrospinal fluid (CSF) on droplet digital polymerase chain reaction assay.	ibrutinib	57-66	MYD88 innate immune signal transduction adaptor	Homo sapiens	181-186
33661190-13	2021	Ibrutinib significantly suppressed proliferating (Ki67+) CD19+ peripheral blood mononuclear cells and had no significant effect on other lymphocyte subsets.	ibrutinib	0-9	CD19 molecule	Homo sapiens	57-61
33735664-2	2021	Treatment for WM/LPL is highly variable in clinic and ibrutinib (a Bruton tyrosine kinase inhibitor, BTKi) has become a new treatment option for WM.	ibrutinib	54-63	inhibitor of Bruton tyrosine kinase	Homo sapiens	101-105
33328281-6	2021	Importantly, various studies confirmed empirically that administration of BTK inhibitors (Acalabrutinib and Ibrutinib) decreased the duration of mechanical ventilation and mortality rate for hospitalized patients with severe COVID-19.	ibrutinib	108-117	Bruton tyrosine kinase	Homo sapiens	74-77
33735664-9	2021	Ibrutinib/BTKi showed potential benefit in relapsed/refractory patients and patients without CXCR4NS/MS including those with TP53 mutations.	ibrutinib	0-9	C-X-C motif chemokine receptor 4	Homo sapiens	93-98
33735664-9	2021	Ibrutinib/BTKi showed potential benefit in relapsed/refractory patients and patients without CXCR4NS/MS including those with TP53 mutations.	ibrutinib	0-9	tumor protein p53	Homo sapiens	125-129
33011863-0	2021	ALK-positive histiocytosis associated with chronic lymphocytic leukaemia/small lymphocytic lymphoma: a multitarget response under ibrutinib.	ibrutinib	130-139	ALK receptor tyrosine kinase	Homo sapiens	0-3
33011863-7	2021	Moreover, both tumours eradication under ibrutinib suggests that BTK inhibitors may also be effective in histiocytic neoplasms.	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	65-68
33786575-9	2021	This is important during ibrutinib therapy since CLL cells induce the FoxO1-GAB1-pAKT axis, which represents an adaptation mechanism to the inability to home to immune niches.	ibrutinib	25-34	forkhead box O1	Homo sapiens	70-75
33786575-9	2021	This is important during ibrutinib therapy since CLL cells induce the FoxO1-GAB1-pAKT axis, which represents an adaptation mechanism to the inability to home to immune niches.	ibrutinib	25-34	GRB2 associated binding protein 1	Homo sapiens	76-80
33786575-11	2021	GAB1 inhibitors induce CLL cell apoptosis, impair cell migration, inhibit "tonic" or BCR-induced AKT phosphorylation, and block compensatory AKT activity during ibrutinib therapy.	ibrutinib	161-170	GRB2 associated binding protein 1	Homo sapiens	0-4
33754642-2	2021	Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	35-57
33792119-0	2021	CDKN1C-mediated growth inhibition by an EZH1/2 dual inhibitor overcomes resistance of mantle cell lymphoma to ibrutinib.	ibrutinib	110-119	cyclin dependent kinase inhibitor 1C	Homo sapiens	0-6
33792119-0	2021	CDKN1C-mediated growth inhibition by an EZH1/2 dual inhibitor overcomes resistance of mantle cell lymphoma to ibrutinib.	ibrutinib	110-119	enhancer of zeste 1 polycomb repressive complex 2 subunit	Homo sapiens	40-46
33792119-5	2021	In an ibrutinib-resistant MCL patient-derived xenograft (PDX) mouse model, OR-S1 treatment by oral administration significantly inhibited MCL tumor growth, whereas ibrutinib did not.	ibrutinib	6-15	olfactory receptor family 11 subfamily H member 4	Mus musculus	75-80
33792119-9	2021	These results suggest that EZH1/2 may be a potential novel target for the treatment of aggressive ibrutinib-resistant MCL via CDKN1C-mediated cell cycle arrest.	ibrutinib	98-107	enhancer of zeste 1 polycomb repressive complex 2 subunit	Homo sapiens	27-33
33792119-9	2021	These results suggest that EZH1/2 may be a potential novel target for the treatment of aggressive ibrutinib-resistant MCL via CDKN1C-mediated cell cycle arrest.	ibrutinib	98-107	cyclin dependent kinase inhibitor 1C	Homo sapiens	126-132
33730844-2	2021	The BTK inhibitor ibrutinib may be intolerable for some patients.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
33734339-1	2021	The BTK inhibitor ibrutinib may protect against pulmonary injury in COVID-19-infected patients.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
33735912-2	2021	To understand the response to BTK inhibitors on a molecular level, we performed (phospho)proteomic analyses under ibrutinib treatment.	ibrutinib	114-123	Bruton tyrosine kinase	Homo sapiens	30-33
33730585-1	2021	Ibrutinib, a bruton"s tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-37
33730585-1	2021	Ibrutinib, a bruton"s tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	39-42
33730585-1	2021	Ibrutinib, a bruton"s tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease.	ibrutinib	170-179	Bruton tyrosine kinase	Homo sapiens	39-42
33746983-12	2021	Combinatorial attack provides a rationale for immunosuppressive therapy of inflammatory cardiomyopathy and provides an in silico prediction that the approved therapeutics, ibrutinib and idelalisib targeting Btk and Pik3cd respectively, could potentially be re-purposed as adjuncts to immunosuppression.	ibrutinib	172-181	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	207-210
33689703-4	2021	Human CLL carrying either IKZF3 mutation or high IKZF3 expression was associated with overexpression of BCR/NF-kappaB pathway members and reduced sensitivity to BCR signaling inhibition by ibrutinib.	ibrutinib	189-198	IKAROS family zinc finger 3	Homo sapiens	26-31
33689703-4	2021	Human CLL carrying either IKZF3 mutation or high IKZF3 expression was associated with overexpression of BCR/NF-kappaB pathway members and reduced sensitivity to BCR signaling inhibition by ibrutinib.	ibrutinib	189-198	IKAROS family zinc finger 3	Homo sapiens	49-54
33746983-12	2021	Combinatorial attack provides a rationale for immunosuppressive therapy of inflammatory cardiomyopathy and provides an in silico prediction that the approved therapeutics, ibrutinib and idelalisib targeting Btk and Pik3cd respectively, could potentially be re-purposed as adjuncts to immunosuppression.	ibrutinib	172-181	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta	Mus musculus	215-221
33663302-0	2021	A single-tube multiplex method for monitoring mutations in cysteine 481 of Bruton Tyrosine Kinase (BTK) gene in chronic lymphocytic leukemia patients treated with ibrutinib.	ibrutinib	163-172	Bruton tyrosine kinase	Homo sapiens	75-97
33688166-2	2021	Ibrutinib is a first-in-class oral Bruton"s tyrosine kinase (BTK) inhibitor which has demonstrated improvements in both progression free (PFS) and overall survival (OS) in both the treatment naive and relapsed/refractory setting as compared to traditional chemoimmunotherapy.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	35-59
33688166-2	2021	Ibrutinib is a first-in-class oral Bruton"s tyrosine kinase (BTK) inhibitor which has demonstrated improvements in both progression free (PFS) and overall survival (OS) in both the treatment naive and relapsed/refractory setting as compared to traditional chemoimmunotherapy.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	61-64
33663302-0	2021	A single-tube multiplex method for monitoring mutations in cysteine 481 of Bruton Tyrosine Kinase (BTK) gene in chronic lymphocytic leukemia patients treated with ibrutinib.	ibrutinib	163-172	Bruton tyrosine kinase	Homo sapiens	99-102
33654205-6	2021	Co-treatment with BET inhibitor or BET-PROTAC and ibrutinib or venetoclax exerted synergistic in vitro lethality in the RT-DLBCL cells.	ibrutinib	50-59	delta/notch like EGF repeat containing	Homo sapiens	35-38
33709472-0	2021	Ibrutinib modulates Abeta/tau pathology, neuroinflammation, and cognitive function in mouse models of Alzheimer"s disease.	ibrutinib	0-9	amyloid beta (A4) precursor protein	Mus musculus	20-25
33709472-3	2021	In 5xFAD mice, ibrutinib injection significantly reduced Abeta plaque levels by promoting the non-amyloidogenic pathway of APP cleavage, decreased Abeta-induced neuroinflammatory responses, and significantly downregulated phosphorylation of tau by reducing levels of phosphorylated cyclin-dependent kinase-5 (p-CDK5).	ibrutinib	15-24	amyloid beta (A4) precursor protein	Mus musculus	57-62
33709472-3	2021	In 5xFAD mice, ibrutinib injection significantly reduced Abeta plaque levels by promoting the non-amyloidogenic pathway of APP cleavage, decreased Abeta-induced neuroinflammatory responses, and significantly downregulated phosphorylation of tau by reducing levels of phosphorylated cyclin-dependent kinase-5 (p-CDK5).	ibrutinib	15-24	amyloid beta (A4) precursor protein	Mus musculus	147-152
33709472-3	2021	In 5xFAD mice, ibrutinib injection significantly reduced Abeta plaque levels by promoting the non-amyloidogenic pathway of APP cleavage, decreased Abeta-induced neuroinflammatory responses, and significantly downregulated phosphorylation of tau by reducing levels of phosphorylated cyclin-dependent kinase-5 (p-CDK5).	ibrutinib	15-24	cyclin-dependent kinase 5	Mus musculus	282-307
33709472-3	2021	In 5xFAD mice, ibrutinib injection significantly reduced Abeta plaque levels by promoting the non-amyloidogenic pathway of APP cleavage, decreased Abeta-induced neuroinflammatory responses, and significantly downregulated phosphorylation of tau by reducing levels of phosphorylated cyclin-dependent kinase-5 (p-CDK5).	ibrutinib	15-24	cyclin-dependent kinase 5	Mus musculus	311-315
33273263-1	2021	: Ibrutinib is the first clinically approved inhibitor of Bruton"s tyrosine kinase, an essential enzyme for survival and proliferation of B cells by activating the B-cell receptor-signalling pathway.	ibrutinib	2-11	Bruton tyrosine kinase	Homo sapiens	58-82
32336682-6	2021	On the contrary, suppression of oxidative stress and the BTK inhibitor Ibrutinib negated SCF levels.	ibrutinib	71-80	Bruton tyrosine kinase	Homo sapiens	57-60
33190294-1	2021	BACKGROUND: Ibrutinib, an inhibitor of the Bruton"s kinase (BTK), is characterized by high efficacy in the therapy of patients with relapsed and refractory chronic lymphocytic leukemia (RR-CLL).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	43-58
33190294-1	2021	BACKGROUND: Ibrutinib, an inhibitor of the Bruton"s kinase (BTK), is characterized by high efficacy in the therapy of patients with relapsed and refractory chronic lymphocytic leukemia (RR-CLL).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	60-63
32336682-6	2021	On the contrary, suppression of oxidative stress and the BTK inhibitor Ibrutinib negated SCF levels.	ibrutinib	71-80	KIT ligand	Homo sapiens	89-92
33640903-12	2021	These results demonstrate that ibrutinib effectively inhibits the CSCs-like phenotype of OSCC cells through dysregulation of BTK/CD133 signaling.	ibrutinib	31-40	Bruton tyrosine kinase	Homo sapiens	125-128
32782382-9	2021	Overall, Ibrutinib and R-BAC were associated with improved median PFS-2 [24 and 25 months, respectively], compared to R-B (13) or others (7).	ibrutinib	9-18	GINS complex subunit 2	Homo sapiens	66-71
33434619-3	2021	The clinical success of ibrutinib, an inhibitor of Bruton tyrosine kinase, in the treatment of mantle cell lymphomas following its approval in 2013 helped to overcome a general bias against the development of irreversible drug inhibitors.	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	51-73
33640903-12	2021	These results demonstrate that ibrutinib effectively inhibits the CSCs-like phenotype of OSCC cells through dysregulation of BTK/CD133 signaling.	ibrutinib	31-40	prominin 1	Homo sapiens	129-134
33718939-1	2021	The therapeutic landscape of chronic lymphocytic leukemia (CLL) underwent a paradigm shift in 2014 with the approval of ibrutinib, which binds covalently to the C481 residue of Bruton"s tyrosine kinase (BTK) and irreversibly inhibits it.	ibrutinib	120-129	Bruton tyrosine kinase	Homo sapiens	177-201
33718939-1	2021	The therapeutic landscape of chronic lymphocytic leukemia (CLL) underwent a paradigm shift in 2014 with the approval of ibrutinib, which binds covalently to the C481 residue of Bruton"s tyrosine kinase (BTK) and irreversibly inhibits it.	ibrutinib	120-129	Bruton tyrosine kinase	Homo sapiens	203-206
33629212-0	2021	Identification BCL6 and miR-30 family associating with Ibrutinib resistance in activated B-cell-like diffuse large B-cell lymphoma.	ibrutinib	55-64	BCL6 transcription repressor	Homo sapiens	15-19
33640875-14	2021	The Bruton"s tyrosine kinase inhibitor ibrutinib and the B-cell lymphoma 2 inhibitor venetoclax can be used increasingly in earlier lines of treatment with improved progression-free survival.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	4-28
33668876-6	2021	The observed upregulation of B cell receptor signaling, crosstalk with the microenvironment, upregulation of CD52, and metabolic reprogramming towards dependence on oxidative phosphorylation favor resistance to ibrutinib treatment.	ibrutinib	211-220	CD52 molecule	Homo sapiens	109-113
33629212-4	2021	First, two expression profiles were downloaded from the GEO database, which used to identify the DEGs related to Ibrutinib resistance in ABC-DLBCL cell lines by GEO2R analysis separately.	ibrutinib	113-122	delta 4-desaturase, sphingolipid 1	Homo sapiens	97-101
33629212-10	2021	In addition, another expression profile from GEO database showed that BCL6 was significantly high expression in no responsive patients after Ibrutinib treatment, and the receiver operating characteristic (ROC) curve which was used to evaluate the relationship between BCL6 expression and its effect was 0.67.	ibrutinib	141-150	BCL6 transcription repressor	Homo sapiens	70-74
33629212-11	2021	MTT assay showed that treatment with FX1 (a BCL6 inhibitor) can enhance the sensitivity of Ibrutinib in C481S BTK HBL-1 cells.	ibrutinib	91-100	BCL6 transcription repressor	Homo sapiens	44-48
33629212-12	2021	The results suggested that BCL6 and miR-30 family maybe associate with Ibrutinib resistance in ABC-DLBCL.	ibrutinib	71-80	BCL6 transcription repressor	Homo sapiens	27-31
33181832-2	2021	OAsIs (NCT02558816), a single-arm multi-center prospective phase I/II trial, aimed to determine the maximum tolerated dose (MTD) of venetoclax in combination with fixed doses of ibrutinib and obinutuzumab, in relapsed MCL patients.	ibrutinib	178-187	cAMP responsive element binding protein 3 like 1	Homo sapiens	0-5
33714285-6	2021	We found that ibrutinib combined with DXMS increased the apoptosis of MM cell lines through the PI3K/PARP pathway, significantly reduced CD38 expression in MM cells from patients in vitro, and reduced tumor size and increased the survival time in mice model.	ibrutinib	14-23	poly(ADP-ribose) polymerase 1	Homo sapiens	101-105
33714285-6	2021	We found that ibrutinib combined with DXMS increased the apoptosis of MM cell lines through the PI3K/PARP pathway, significantly reduced CD38 expression in MM cells from patients in vitro, and reduced tumor size and increased the survival time in mice model.	ibrutinib	14-23	CD38 molecule	Homo sapiens	137-141
33602908-1	2021	Ibrutinib inhibits Bruton tyrosine kinase while venetoclax is a specific inhibitor of the anti-apoptotic protein BCL2.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	19-41
33669187-3	2021	Ibrutinib, an irreversible molecular inhibitor of BTK, has been widely studied in B cell malignancies, and recently, this drug is repurposed for the treatment of solid tumors.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	50-53
33669187-5	2021	Moreover, in vitro treatment of murine MDSCs with ibrutinib altered NO production, decreased mRNA expression of Ido, Arg, Tgfbeta, and displayed defects in T-cell suppression.	ibrutinib	50-59	indoleamine 2,3-dioxygenase 1	Mus musculus	112-115
33669187-5	2021	Moreover, in vitro treatment of murine MDSCs with ibrutinib altered NO production, decreased mRNA expression of Ido, Arg, Tgfbeta, and displayed defects in T-cell suppression.	ibrutinib	50-59	transforming growth factor alpha	Mus musculus	122-129
33181270-5	2021	Our results showed that ibrutinib treatment significantly reduced lipopolysaccharide (LPS)-induced depressive-like behaviors and neuroinflammation via inhibiting NF-kB activation, decreasing proinflammatory cytokine levels, and normalizing redox signaling and its downstream components, including Nrf2, HO-1, and SOD2, as well as glial cell activation markers, such as Iba-1 and GFAP.	ibrutinib	24-33	nuclear factor, erythroid derived 2, like 2	Mus musculus	297-301
33669187-6	2021	Consistent with these findings, in vivo inhibition of BTK with ibrutinib resulted in reduced MDSC-mediated immune suppression, increased CD8+ T cell infiltration, decreased tumor growth, and improved response to anti-PDL1 checkpoint inhibitor therapy in a murine model of NB.	ibrutinib	63-72	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	54-57
33669187-6	2021	Consistent with these findings, in vivo inhibition of BTK with ibrutinib resulted in reduced MDSC-mediated immune suppression, increased CD8+ T cell infiltration, decreased tumor growth, and improved response to anti-PDL1 checkpoint inhibitor therapy in a murine model of NB.	ibrutinib	63-72	CD274 antigen	Mus musculus	217-221
33669329-2	2021	Thus, up to 40% of all patients with Waldenstrom"s macroglobulinemia (WM) carry an activating mutation of CXCR4 that leads to a more aggressive clinical course and inferior outcome upon treatment with the Bruton"s tyrosine kinase inhibitor ibrutinib.	ibrutinib	240-249	C-X-C motif chemokine receptor 4	Homo sapiens	106-111
33669329-2	2021	Thus, up to 40% of all patients with Waldenstrom"s macroglobulinemia (WM) carry an activating mutation of CXCR4 that leads to a more aggressive clinical course and inferior outcome upon treatment with the Bruton"s tyrosine kinase inhibitor ibrutinib.	ibrutinib	240-249	Bruton tyrosine kinase	Homo sapiens	205-229
33181270-5	2021	Our results showed that ibrutinib treatment significantly reduced lipopolysaccharide (LPS)-induced depressive-like behaviors and neuroinflammation via inhibiting NF-kB activation, decreasing proinflammatory cytokine levels, and normalizing redox signaling and its downstream components, including Nrf2, HO-1, and SOD2, as well as glial cell activation markers, such as Iba-1 and GFAP.	ibrutinib	24-33	heme oxygenase 1	Mus musculus	303-307
33181270-5	2021	Our results showed that ibrutinib treatment significantly reduced lipopolysaccharide (LPS)-induced depressive-like behaviors and neuroinflammation via inhibiting NF-kB activation, decreasing proinflammatory cytokine levels, and normalizing redox signaling and its downstream components, including Nrf2, HO-1, and SOD2, as well as glial cell activation markers, such as Iba-1 and GFAP.	ibrutinib	24-33	superoxide dismutase 2, mitochondrial	Mus musculus	313-317
33181270-5	2021	Our results showed that ibrutinib treatment significantly reduced lipopolysaccharide (LPS)-induced depressive-like behaviors and neuroinflammation via inhibiting NF-kB activation, decreasing proinflammatory cytokine levels, and normalizing redox signaling and its downstream components, including Nrf2, HO-1, and SOD2, as well as glial cell activation markers, such as Iba-1 and GFAP.	ibrutinib	24-33	induction of brown adipocytes 1	Mus musculus	369-374
33181270-5	2021	Our results showed that ibrutinib treatment significantly reduced lipopolysaccharide (LPS)-induced depressive-like behaviors and neuroinflammation via inhibiting NF-kB activation, decreasing proinflammatory cytokine levels, and normalizing redox signaling and its downstream components, including Nrf2, HO-1, and SOD2, as well as glial cell activation markers, such as Iba-1 and GFAP.	ibrutinib	24-33	glial fibrillary acidic protein	Mus musculus	379-383
33181270-6	2021	Further, ibrutinib treatment inhibited LPS-activated inflammasome activation by targeting NLRP3/P38/Caspase-1 signaling.	ibrutinib	9-18	NLR family, pyrin domain containing 3	Mus musculus	90-95
33181270-6	2021	Further, ibrutinib treatment inhibited LPS-activated inflammasome activation by targeting NLRP3/P38/Caspase-1 signaling.	ibrutinib	9-18	synaptophysin	Mus musculus	96-99
33181270-6	2021	Further, ibrutinib treatment inhibited LPS-activated inflammasome activation by targeting NLRP3/P38/Caspase-1 signaling.	ibrutinib	9-18	caspase 1	Mus musculus	100-109
33181270-7	2021	Interestingly, LPS reduced the number of dendritic spines and expression of BDNF, and synaptic-related markers, including PSD95, snap25, and synaptophysin, were improved by ibrutinib treatment in the hippocampal area of the mouse brain.	ibrutinib	173-182	brain derived neurotrophic factor	Mus musculus	76-80
33181270-7	2021	Interestingly, LPS reduced the number of dendritic spines and expression of BDNF, and synaptic-related markers, including PSD95, snap25, and synaptophysin, were improved by ibrutinib treatment in the hippocampal area of the mouse brain.	ibrutinib	173-182	discs large MAGUK scaffold protein 4	Mus musculus	122-127
33181270-7	2021	Interestingly, LPS reduced the number of dendritic spines and expression of BDNF, and synaptic-related markers, including PSD95, snap25, and synaptophysin, were improved by ibrutinib treatment in the hippocampal area of the mouse brain.	ibrutinib	173-182	synaptosomal-associated protein 25	Mus musculus	129-135
33181270-7	2021	Interestingly, LPS reduced the number of dendritic spines and expression of BDNF, and synaptic-related markers, including PSD95, snap25, and synaptophysin, were improved by ibrutinib treatment in the hippocampal area of the mouse brain.	ibrutinib	173-182	synaptophysin	Mus musculus	141-154
33089525-7	2021	Here we describe a patient who was found to harbor a novel somatic variant of PLCG2 and experienced a lack of treatment response to both ibrutinib and entospletinib.	ibrutinib	137-146	phospholipase C gamma 2	Homo sapiens	78-83
32961571-1	2021	Ibrutinib, an irreversible inhibitor of Bruton"s tyrosine kinase, has a favorable safety profile in patients with B cell-related malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	40-64
32978866-3	2021	Thirteen months after the initiation of ibrutinib (a Bruton"s tyrosine kinase inhibitor), the patient"s alanine aminotransferase (ALT) levels suddenly increased to 427 U/L.	ibrutinib	40-49	Bruton tyrosine kinase	Homo sapiens	53-77
32978866-3	2021	Thirteen months after the initiation of ibrutinib (a Bruton"s tyrosine kinase inhibitor), the patient"s alanine aminotransferase (ALT) levels suddenly increased to 427 U/L.	ibrutinib	40-49	glutamic--pyruvic transaminase	Homo sapiens	104-128
32623551-5	2021	Ibrutinib has unexplained nephrotoxicity and high metabolite concentrations are also found in kidneys of Cyp3a knockout mice.	ibrutinib	0-9	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	105-110
32623551-8	2021	Ibrutinib-mediated toxicity was enhanced in-vitro by inhibitors of breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and multidrug resistance protein (MRP).	ibrutinib	0-9	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	67-99
32623551-8	2021	Ibrutinib-mediated toxicity was enhanced in-vitro by inhibitors of breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and multidrug resistance protein (MRP).	ibrutinib	0-9	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	101-105
32623551-8	2021	Ibrutinib-mediated toxicity was enhanced in-vitro by inhibitors of breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and multidrug resistance protein (MRP).	ibrutinib	0-9	ATP binding cassette subfamily B member 1	Homo sapiens	108-122
32623551-8	2021	Ibrutinib-mediated toxicity was enhanced in-vitro by inhibitors of breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and multidrug resistance protein (MRP).	ibrutinib	0-9	ATP binding cassette subfamily B member 1	Homo sapiens	124-128
32623551-8	2021	Ibrutinib-mediated toxicity was enhanced in-vitro by inhibitors of breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and multidrug resistance protein (MRP).	ibrutinib	0-9	ATP binding cassette subfamily C member 1	Homo sapiens	134-162
32623551-8	2021	Ibrutinib-mediated toxicity was enhanced in-vitro by inhibitors of breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and multidrug resistance protein (MRP).	ibrutinib	0-9	ATP binding cassette subfamily C member 1	Homo sapiens	164-167
33273682-5	2021	These data have shed light on the essential role of CXCR4 in this disease and have paved the way to use these findings for predicting treatment response to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and novel therapeutic approaches in WM, which might be transferable to other related CXCR4 positive diseases.	ibrutinib	199-208	Bruton tyrosine kinase	Homo sapiens	160-182
33273682-5	2021	These data have shed light on the essential role of CXCR4 in this disease and have paved the way to use these findings for predicting treatment response to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and novel therapeutic approaches in WM, which might be transferable to other related CXCR4 positive diseases.	ibrutinib	199-208	Bruton tyrosine kinase	Homo sapiens	184-187
33796237-1	2021	Ibrutinib, the first in class of the oral covalent Bruton tyrosine kinase (BTK) inhibitors, has profoundly changed the treatment landscape of chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	51-73
33796237-1	2021	Ibrutinib, the first in class of the oral covalent Bruton tyrosine kinase (BTK) inhibitors, has profoundly changed the treatment landscape of chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	75-78
32683672-7	2021	The B-cell receptor inhibitor ibrutinib targeting bruton tyrosine kinase (BTK) is approved for the treatment of CLL.	ibrutinib	30-39	Bruton tyrosine kinase	Homo sapiens	50-72
33995994-0	2021	Mechanism of covalent binding of ibrutinib to Bruton"s tyrosine kinase revealed by QM/MM calculations.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	46-70
33995994-1	2021	Ibrutinib is the first covalent inhibitor of Bruton"s tyrosine kinase (BTK) to be used in the treatment of B-cell cancers.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	45-69
33995994-1	2021	Ibrutinib is the first covalent inhibitor of Bruton"s tyrosine kinase (BTK) to be used in the treatment of B-cell cancers.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	71-74
33995994-4	2021	We investigate several mechanisms of covalent modification of C481 in BTK by ibrutinib using combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics reaction simulations.	ibrutinib	77-86	Bruton tyrosine kinase	Homo sapiens	70-73
33995994-6	2021	There is a subsequent rate-limiting keto-enol tautomerisation step (DeltaG   = 10.5 kcal mol-1) to reach the inactivated BTK/ibrutinib complex.	ibrutinib	125-134	Bruton tyrosine kinase	Homo sapiens	121-124
33995994-7	2021	Our results represent the first mechanistic study of BTK inactivation by ibrutinib to consider multiple mechanistic pathways.	ibrutinib	73-82	Bruton tyrosine kinase	Homo sapiens	53-56
33467441-7	2021	Ibrutinib achieves a reduction in the production of TNFalpha, IL1, IL-6 and Monocyte chemo-attractant protein-1 (MCP-1) by neutrophils and macrophages, that are key players in keeping the inflammatory process.	ibrutinib	0-9	tumor necrosis factor	Homo sapiens	52-60
33467441-7	2021	Ibrutinib achieves a reduction in the production of TNFalpha, IL1, IL-6 and Monocyte chemo-attractant protein-1 (MCP-1) by neutrophils and macrophages, that are key players in keeping the inflammatory process.	ibrutinib	0-9	interleukin 1 alpha	Homo sapiens	62-65
33467441-7	2021	Ibrutinib achieves a reduction in the production of TNFalpha, IL1, IL-6 and Monocyte chemo-attractant protein-1 (MCP-1) by neutrophils and macrophages, that are key players in keeping the inflammatory process.	ibrutinib	0-9	interleukin 6	Homo sapiens	67-71
33467441-7	2021	Ibrutinib achieves a reduction in the production of TNFalpha, IL1, IL-6 and Monocyte chemo-attractant protein-1 (MCP-1) by neutrophils and macrophages, that are key players in keeping the inflammatory process.	ibrutinib	0-9	C-C motif chemokine ligand 2	Homo sapiens	76-111
33467441-7	2021	Ibrutinib achieves a reduction in the production of TNFalpha, IL1, IL-6 and Monocyte chemo-attractant protein-1 (MCP-1) by neutrophils and macrophages, that are key players in keeping the inflammatory process.	ibrutinib	0-9	C-C motif chemokine ligand 2	Homo sapiens	113-118
32683672-7	2021	The B-cell receptor inhibitor ibrutinib targeting bruton tyrosine kinase (BTK) is approved for the treatment of CLL.	ibrutinib	30-39	Bruton tyrosine kinase	Homo sapiens	74-77
32683672-8	2021	Besides BTK, ibrutinib additionally inhibits interleukin-2-inducible T cell kinase (ITK) which is involved in T cell differentiation.	ibrutinib	13-22	IL2 inducible T cell kinase	Homo sapiens	45-82
32683672-8	2021	Besides BTK, ibrutinib additionally inhibits interleukin-2-inducible T cell kinase (ITK) which is involved in T cell differentiation.	ibrutinib	13-22	IL2 inducible T cell kinase	Homo sapiens	84-87
32683672-12	2021	Furthermore, ibrutinib enriched CART cells with less-differentiated naive-like phenotype and decreased expression of exhaustion markers including PD-1, TIM-3, and LAG-3.	ibrutinib	13-22	programmed cell death 1	Homo sapiens	146-150
32683672-12	2021	Furthermore, ibrutinib enriched CART cells with less-differentiated naive-like phenotype and decreased expression of exhaustion markers including PD-1, TIM-3, and LAG-3.	ibrutinib	13-22	hepatitis A virus cellular receptor 2	Homo sapiens	152-157
32683672-12	2021	Furthermore, ibrutinib enriched CART cells with less-differentiated naive-like phenotype and decreased expression of exhaustion markers including PD-1, TIM-3, and LAG-3.	ibrutinib	13-22	lymphocyte activating 3	Homo sapiens	163-168
32683672-14	2021	In summary, BTK/ITK inhibition with ibrutinib during CART cell culture can improve yield and function of CLL patient-derived CART cell products.	ibrutinib	36-45	Bruton tyrosine kinase	Homo sapiens	12-15
32683672-14	2021	In summary, BTK/ITK inhibition with ibrutinib during CART cell culture can improve yield and function of CLL patient-derived CART cell products.	ibrutinib	36-45	IL2 inducible T cell kinase	Homo sapiens	16-19
33441177-2	2021	Recently, BTK inhibitors acalabrutinib and ibrutinib have been found to protect against pulmonary injury in a small group of patients infected with SARS-CoV-2.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	10-13
33519491-0	2020	The Bruton"s Tyrosine Kinase Inhibitor Ibrutinib Impairs the Vascular Development of Zebrafish Larvae.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	4-28
33519491-1	2020	Ibrutinib is an orally bioavailable, irreversible selective Bruton"s tyrosine kinase inhibitor that has demonstrated impressive therapeutic effects in patients with B cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	60-84
33441177-4	2021	Understanding the potential mechanism of action of BTK inhibition in SARS-CoV-2 is clearly of importance to determine how acalabrutinib, ibrutinib and possibly other BTK inhibitors may provide protection against lung injury.	ibrutinib	137-146	Bruton tyrosine kinase	Homo sapiens	51-54
33570649-8	2021	Next-generation inhibitors and bispecific antibodies have the potential to overcome resistance to the BTK inhibitor ibrutinib.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	102-105
33570628-1	2021	Inhibition of the B-cell receptor (BCR) signaling pathway is highly effective in B-cell neoplasia through Bruton tyrosine kinase inhibition by ibrutinib.	ibrutinib	143-152	Bruton tyrosine kinase	Homo sapiens	106-128
32979005-1	2021	Ibrutinib was an FDA-approved drug to treat B-lymphoid malignancies, which mechanistically functions as a covalent inhibitor for Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	129-153
33570628-6	2021	Among the differentially expressed genes, RAC2, part of the BCR signature and a known regulator of cell adhesion, was downregulated at both the RNA and protein levels by ibrutinib only in sensitive cells.	ibrutinib	170-179	Rac family small GTPase 2	Homo sapiens	42-46
33570628-8	2021	RAC2 reduction using RNA interference and CRISPR impaired cell adhesion, whereas RAC2 overexpression reversed ibrutinib-induced cell adhesion impairment.	ibrutinib	110-119	Rac family small GTPase 2	Homo sapiens	81-85
33570628-9	2021	In a xenograft mouse model, mice treated with ibrutinib exhibited slower tumor growth, with reduced RAC2 expression in tissue.	ibrutinib	46-55	Rac family small GTPase 2	Mus musculus	100-104
33570628-10	2021	Finally, RAC2 was expressed in ~65% of human primary MCL tumors, and RAC2 suppression by ibrutinib resulted in cell adhesion impairment.	ibrutinib	89-98	Rac family small GTPase 2	Homo sapiens	69-73
32979005-1	2021	Ibrutinib was an FDA-approved drug to treat B-lymphoid malignancies, which mechanistically functions as a covalent inhibitor for Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	155-158
32979005-2	2021	During the course of screening more potent and selective BTK inhibitors, we discovered that, MM2-48, an Ibrutinib analogue which contains the alkynyl amide functional group in place of the acrylamide warhead, exhibits a much stronger cytotoxicity.	ibrutinib	104-113	Bruton tyrosine kinase	Homo sapiens	57-60
33159967-0	2021	A multi-kinase inhibitor APG-2449 enhances the antitumor effect of Ibrutinib in esophageal squamous cell carcinoma via EGFR/FAK pathway inhibition.	ibrutinib	67-76	epidermal growth factor receptor	Homo sapiens	119-123
33159967-0	2021	A multi-kinase inhibitor APG-2449 enhances the antitumor effect of Ibrutinib in esophageal squamous cell carcinoma via EGFR/FAK pathway inhibition.	ibrutinib	67-76	protein tyrosine kinase 2	Homo sapiens	124-127
33159967-2	2021	It has been reported that ibrutinib possesses anticancer activity in ESCC with MYC and/or ERBB2 amplification.	ibrutinib	26-35	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	79-82
33159967-2	2021	It has been reported that ibrutinib possesses anticancer activity in ESCC with MYC and/or ERBB2 amplification.	ibrutinib	26-35	erb-b2 receptor tyrosine kinase 2	Homo sapiens	90-95
33159967-8	2021	In terms of mechanism, ibrutinib alone could decrease the phosphorylation level of EGFR and its downstream pathway of MEK/ERK.	ibrutinib	23-32	epidermal growth factor receptor	Homo sapiens	83-87
33159967-8	2021	In terms of mechanism, ibrutinib alone could decrease the phosphorylation level of EGFR and its downstream pathway of MEK/ERK.	ibrutinib	23-32	mitogen-activated protein kinase kinase 7	Homo sapiens	118-121
33159967-8	2021	In terms of mechanism, ibrutinib alone could decrease the phosphorylation level of EGFR and its downstream pathway of MEK/ERK.	ibrutinib	23-32	mitogen-activated protein kinase 1	Homo sapiens	122-125
33159967-9	2021	The combination therapy of APG-2449 and ibrutinib could significantly down-regulate the phosphorylation level of MEK/ERK and AKT.	ibrutinib	40-49	mitogen-activated protein kinase kinase 7	Homo sapiens	113-116
33159967-9	2021	The combination therapy of APG-2449 and ibrutinib could significantly down-regulate the phosphorylation level of MEK/ERK and AKT.	ibrutinib	40-49	mitogen-activated protein kinase 1	Homo sapiens	117-120
33159967-9	2021	The combination therapy of APG-2449 and ibrutinib could significantly down-regulate the phosphorylation level of MEK/ERK and AKT.	ibrutinib	40-49	AKT serine/threonine kinase 1	Homo sapiens	125-128
33082556-9	2021	Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib.	ibrutinib	136-145	homeobox A4	Homo sapiens	17-22
33168411-8	2021	Treatment with BTK inhibitor, Ibrutinib causes attenuation in AKI associated dysfunction in biochemical parameters (serum creatinine/blood urea nitrogen, renal myeloperoxidase activity) and oxidative stress in immune cells and kidney (iNOS/NOX2/lipid peroxides/nitrotyrosine/protein carbonyls).	ibrutinib	30-39	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	15-18
33272709-4	2021	In particular, 11a and 11b exhibited stronger antiproliferative activity against AML and B lymphomas cell lines compared with BTK inhibitor ibrutinib and showed low cytotoxicity against normal peripheral blood mononuclear cells (PBMCs).	ibrutinib	140-149	Bruton tyrosine kinase	Homo sapiens	126-129
31949019-2	2021	In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCgamma2 in human platelets.	ibrutinib	67-76	Bruton tyrosine kinase	Homo sapiens	53-56
31949019-2	2021	In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCgamma2 in human platelets.	ibrutinib	67-76	C-type lectin domain family 1 member B	Homo sapiens	83-89
31949019-2	2021	In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCgamma2 in human platelets.	ibrutinib	67-76	spleen associated tyrosine kinase	Homo sapiens	149-152
31949019-2	2021	In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCgamma2 in human platelets.	ibrutinib	67-76	phospholipase C gamma 2	Homo sapiens	157-166
31949019-4	2021	In contrast, the response to GPVI is delayed in the presence of low concentrations of ibrutinib or in patients with XLA, and tyrosine phosphorylation of Syk is preserved.	ibrutinib	86-95	glycoprotein VI platelet	Homo sapiens	29-33
31949019-7	2021	This feedback role is not seen in mouse platelets and, consistent with this, CLEC-2-mediated activation is blocked by high but not by low concentrations of ibrutinib.	ibrutinib	156-165	C-type lectin domain family 1, member b	Mus musculus	77-83
33168411-8	2021	Treatment with BTK inhibitor, Ibrutinib causes attenuation in AKI associated dysfunction in biochemical parameters (serum creatinine/blood urea nitrogen, renal myeloperoxidase activity) and oxidative stress in immune cells and kidney (iNOS/NOX2/lipid peroxides/nitrotyrosine/protein carbonyls).	ibrutinib	30-39	nitric oxide synthase 2, inducible	Mus musculus	235-239
33168411-8	2021	Treatment with BTK inhibitor, Ibrutinib causes attenuation in AKI associated dysfunction in biochemical parameters (serum creatinine/blood urea nitrogen, renal myeloperoxidase activity) and oxidative stress in immune cells and kidney (iNOS/NOX2/lipid peroxides/nitrotyrosine/protein carbonyls).	ibrutinib	30-39	cytochrome b-245, beta polypeptide	Mus musculus	240-244
33168411-8	2021	Treatment with BTK inhibitor, Ibrutinib causes attenuation in AKI associated dysfunction in biochemical parameters (serum creatinine/blood urea nitrogen, renal myeloperoxidase activity) and oxidative stress in immune cells and kidney (iNOS/NOX2/lipid peroxides/nitrotyrosine/protein carbonyls).	ibrutinib	30-39	myeloperoxidase	Mus musculus	160-175
33322571-0	2020	Bruton"s Tyrosine Kinase Inhibitors Ibrutinib and Acalabrutinib Counteract Anthracycline Resistance in Cancer Cells Expressing AKR1C3.	ibrutinib	36-45	Bruton tyrosine kinase	Homo sapiens	0-24
33552659-2	2021	Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a first-line treatment option, and recent data suggest that strict adherence is directly related to clinical outcomes.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	40-62
33552659-2	2021	Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a first-line treatment option, and recent data suggest that strict adherence is directly related to clinical outcomes.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	64-67
32640487-4	2021	Here, we summarize the current knowledge of BTK/IL-2-inducible T-cell kinase (ITK) signaling in immunopathology and lymphopenia and discuss the potential of BTK/ITK dual inhibitors such as ibrutinib in modulating immunopathology and lymphopenia, for COVID-19 therapy.	ibrutinib	189-198	Bruton tyrosine kinase	Homo sapiens	157-160
32640487-4	2021	Here, we summarize the current knowledge of BTK/IL-2-inducible T-cell kinase (ITK) signaling in immunopathology and lymphopenia and discuss the potential of BTK/ITK dual inhibitors such as ibrutinib in modulating immunopathology and lymphopenia, for COVID-19 therapy.	ibrutinib	189-198	IL2 inducible T cell kinase	Homo sapiens	161-164
33303706-1	2020	Background: Ibrutinib is an oral irreversible Bruton"s tyrosine kinase inhibitor.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	46-70
33092403-0	2020	Ibrutinib-Mediated Atrial Fibrillation Due to Inhibition of CSK.	ibrutinib	0-9	c-src tyrosine kinase	Mus musculus	60-63
33092403-1	2020	Background: Ibrutinib is a Bruton"s tyrosine kinase (BTK) inhibitor with remarkable efficacy against B-cell cancers.	ibrutinib	12-21	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	27-51
33092403-1	2020	Background: Ibrutinib is a Bruton"s tyrosine kinase (BTK) inhibitor with remarkable efficacy against B-cell cancers.	ibrutinib	12-21	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	53-56
33092403-8	2020	Chemoproteomic profiling identified a short list of candidate kinases that was narrowed by additional experimentation leaving C-terminal src kinase (CSK) as the strongest candidate for ibrutinib induced AF.	ibrutinib	185-194	c-src tyrosine kinase	Mus musculus	126-147
33092403-8	2020	Chemoproteomic profiling identified a short list of candidate kinases that was narrowed by additional experimentation leaving C-terminal src kinase (CSK) as the strongest candidate for ibrutinib induced AF.	ibrutinib	185-194	c-src tyrosine kinase	Mus musculus	149-152
33092403-9	2020	Cardiac specific Csk knockout in mice led to increased AF, left atrial enlargement, fibrosis, and inflammation, phenocopying ibrutinib treatment.	ibrutinib	125-134	c-src tyrosine kinase	Mus musculus	17-20
33092403-11	2020	Conclusions: These data identify Csk inhibition as the mechanism by which ibrutinib leads to AF.	ibrutinib	74-83	c-src tyrosine kinase	Mus musculus	33-36
32603412-0	2020	Changes in Bcl-2 members in response to ibrutinib or venetoclax uncover functional hierarchy in determining resistance to venetoclax in CLL.	ibrutinib	40-49	BCL2 apoptosis regulator	Homo sapiens	11-16
32603412-3	2020	Since ibrutinib forces CLL cells out of the LN, we hypothesized that ibrutinib may thereby affect expression of Bcl-XL and Mcl-1 and sensitize CLL cells to venetoclax.	ibrutinib	69-78	BCL2 like 1	Homo sapiens	112-118
32603412-3	2020	Since ibrutinib forces CLL cells out of the LN, we hypothesized that ibrutinib may thereby affect expression of Bcl-XL and Mcl-1 and sensitize CLL cells to venetoclax.	ibrutinib	69-78	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	123-128
32603412-4	2020	We investigated expression of Bcl-2 family members in patients under ibrutinib or venetoclax treatment combined with dissecting functional interactions of Bcl-2 family members in an in vitro model for venetoclax resistance.	ibrutinib	69-78	BCL2 apoptosis regulator	Homo sapiens	30-35
32603412-11	2020	Combined, the data indicate that Bcl-XL is more important in venetoclax resistance than Mcl-1 and provide biological rationale for potential synergy between ibrutinib and venetoclax.	ibrutinib	157-166	BCL2 like 1	Homo sapiens	33-39
32404571-3	2020	In this review article, we discuss current treatment strategies for CLL patients in Japan, where the novel targeted agents, the BTK inhibitor ibrutinib and BCL2 antagonist venetoclax, now are available and increasingly used in clinical practice.	ibrutinib	142-151	Bruton tyrosine kinase	Homo sapiens	128-131
33298182-1	2020	BACKGROUND: Ibrutinib, an irreversible Bruton Tyrosine Kinase (BTK) inhibitor, has revolutionized Chronic Lymphocytic Leukemia (CLL) treatment, but resistances to ibrutinib have emerged, whether related or not to BTK mutations.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	39-61
33298182-1	2020	BACKGROUND: Ibrutinib, an irreversible Bruton Tyrosine Kinase (BTK) inhibitor, has revolutionized Chronic Lymphocytic Leukemia (CLL) treatment, but resistances to ibrutinib have emerged, whether related or not to BTK mutations.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	63-66
33298182-1	2020	BACKGROUND: Ibrutinib, an irreversible Bruton Tyrosine Kinase (BTK) inhibitor, has revolutionized Chronic Lymphocytic Leukemia (CLL) treatment, but resistances to ibrutinib have emerged, whether related or not to BTK mutations.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	213-216
33298182-5	2020	RESULTS: This unveiled that the short clinical relapse of this patient driven by BTK mutation is associated with intraclonal heterogeneity in B leukemic cells and up-regulation of common signaling pathways induced by ibrutinib in both B leukemic cells and immune cells.	ibrutinib	217-226	Bruton tyrosine kinase	Homo sapiens	81-84
33322571-4	2020	In this regard, we demonstrated that Bruton"s tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib efficiently prevented daunorubicin (Dau) inactivation mediated by AKR1C3 in both its recombinant form as well as during its overexpression in cancer cells.	ibrutinib	79-88	Bruton tyrosine kinase	Homo sapiens	37-61
33322571-4	2020	In this regard, we demonstrated that Bruton"s tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib efficiently prevented daunorubicin (Dau) inactivation mediated by AKR1C3 in both its recombinant form as well as during its overexpression in cancer cells.	ibrutinib	79-88	Bruton tyrosine kinase	Homo sapiens	63-66
33322571-4	2020	In this regard, we demonstrated that Bruton"s tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib efficiently prevented daunorubicin (Dau) inactivation mediated by AKR1C3 in both its recombinant form as well as during its overexpression in cancer cells.	ibrutinib	79-88	aldo-keto reductase family 1 member C3	Homo sapiens	173-179
33284944-1	2020	Patients with Waldenstrom macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88WT) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study.	ibrutinib	152-161	MYD88 innate immune signal transduction adaptor	Homo sapiens	85-90
32613545-2	2020	The first-generation inhibitor ibrutinib works by covalent irreversible binding to BTK, a non-receptor tyrosine kinase of the TEC (transient erythroblastopenia of childhood) family that plays a critical role in the B-cell receptor signaling pathway.	ibrutinib	31-40	Bruton tyrosine kinase	Homo sapiens	83-86
32613545-2	2020	The first-generation inhibitor ibrutinib works by covalent irreversible binding to BTK, a non-receptor tyrosine kinase of the TEC (transient erythroblastopenia of childhood) family that plays a critical role in the B-cell receptor signaling pathway.	ibrutinib	31-40	TEC	Homo sapiens	126-129
32613545-2	2020	The first-generation inhibitor ibrutinib works by covalent irreversible binding to BTK, a non-receptor tyrosine kinase of the TEC (transient erythroblastopenia of childhood) family that plays a critical role in the B-cell receptor signaling pathway.	ibrutinib	31-40	TEC	Homo sapiens	131-172
32613545-6	2020	In addition, it has been postulated that ibrutinib-related dermatologic adverse events are mediated by the direct binding to both BTK and other "off-target" kinases.	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	130-133
32705581-6	2020	To evaluate its effect on cellular functions, BTK expression in SK-N-BE(2) and SH-SY5Y neuroblastoma cells was downregulated using gene silencing or inhibition with ibrutinib or acalabrutinib.	ibrutinib	165-174	Bruton tyrosine kinase	Homo sapiens	46-49
33648925-8	2020	In insulin-resistant HepG2 cells (IR-HepG2), ibrutinib inhibited BTK expression in parallel with inflammatory genes, and increased insulin signaling and activity compared with untreated IR-HepG2 cells.	ibrutinib	45-54	insulin	Homo sapiens	3-10
33091668-2	2020	BTK inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies.	ibrutinib	23-32	Bruton tyrosine kinase	Homo sapiens	0-3
33273169-7	2020	Agents such as the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs such as lenalidomide and pomalidomide have shown promising response rates in the relapsed setting.	ibrutinib	58-67	Bruton tyrosine kinase	Homo sapiens	19-41
33273169-7	2020	Agents such as the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs such as lenalidomide and pomalidomide have shown promising response rates in the relapsed setting.	ibrutinib	58-67	Bruton tyrosine kinase	Homo sapiens	43-46
33273175-6	2020	The risk of opportunistic fungal infections, including aspergillosis, is elevated with the Bruton tyrosine kinase inhibitor ibrutinib.	ibrutinib	124-133	Bruton tyrosine kinase	Homo sapiens	91-113
33648925-8	2020	In insulin-resistant HepG2 cells (IR-HepG2), ibrutinib inhibited BTK expression in parallel with inflammatory genes, and increased insulin signaling and activity compared with untreated IR-HepG2 cells.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	65-68
33648925-8	2020	In insulin-resistant HepG2 cells (IR-HepG2), ibrutinib inhibited BTK expression in parallel with inflammatory genes, and increased insulin signaling and activity compared with untreated IR-HepG2 cells.	ibrutinib	45-54	insulin	Homo sapiens	131-138
33297772-2	2020	Novel therapies such as Bruton tyrosine-kinase (BTK) inhibitors have shown to be efficacious in treating WM but with an established, significant toxicity profile seen in the first-generation inhibitor Ibrutinib.	ibrutinib	201-210	Bruton tyrosine kinase	Homo sapiens	24-46
33297772-2	2020	Novel therapies such as Bruton tyrosine-kinase (BTK) inhibitors have shown to be efficacious in treating WM but with an established, significant toxicity profile seen in the first-generation inhibitor Ibrutinib.	ibrutinib	201-210	Bruton tyrosine kinase	Homo sapiens	48-51
32131714-1	2020	Background: Ibrutinib, a first-in-class, once-daily inhibitor of Bruton"s tyrosine kinase (BTK), is approved in the US and EU for the treatment of various B-cell malignancies.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	65-89
32131714-1	2020	Background: Ibrutinib, a first-in-class, once-daily inhibitor of Bruton"s tyrosine kinase (BTK), is approved in the US and EU for the treatment of various B-cell malignancies.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	91-94
33226337-2	2020	Currently approved BTK inhibitors, including Ibrutinib, a first-in-class covalent inhibitor of BTK, bind directly to the kinase active site.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	19-22
32491222-1	2020	Ibrutinib, an irreversible and specific Bruton"s tyrosine kinase (BTK) inhibitor, leads to complete inhibition of IgE/FcepsilonRI-BTK degranulation of human basophils without affecting the signaling via G-protein coupled receptors (C5a, fMLP) [1;2].	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	40-64
32491222-1	2020	Ibrutinib, an irreversible and specific Bruton"s tyrosine kinase (BTK) inhibitor, leads to complete inhibition of IgE/FcepsilonRI-BTK degranulation of human basophils without affecting the signaling via G-protein coupled receptors (C5a, fMLP) [1;2].	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	66-69
32491222-1	2020	Ibrutinib, an irreversible and specific Bruton"s tyrosine kinase (BTK) inhibitor, leads to complete inhibition of IgE/FcepsilonRI-BTK degranulation of human basophils without affecting the signaling via G-protein coupled receptors (C5a, fMLP) [1;2].	ibrutinib	0-9	complement C5a receptor 1	Homo sapiens	232-235
32491222-1	2020	Ibrutinib, an irreversible and specific Bruton"s tyrosine kinase (BTK) inhibitor, leads to complete inhibition of IgE/FcepsilonRI-BTK degranulation of human basophils without affecting the signaling via G-protein coupled receptors (C5a, fMLP) [1;2].	ibrutinib	0-9	formyl peptide receptor 1	Homo sapiens	237-241
32762271-0	2020	Final 5-year findings from the phase 3 HELIOS study of ibrutinib plus bendamustine and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma.	ibrutinib	55-64	IKAROS family zinc finger 2	Homo sapiens	39-45
33226337-2	2020	Currently approved BTK inhibitors, including Ibrutinib, a first-in-class covalent inhibitor of BTK, bind directly to the kinase active site.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	95-98
33226337-5	2020	Additionally, we find that a remote Ibrutinib resistance mutation, T316A in the BTK SH2 domain, drives spurious BTK activity by destabilizing the compact autoinhibitory conformation of full-length BTK, shifting the conformational ensemble away from the autoinhibited form.	ibrutinib	36-45	Bruton tyrosine kinase	Homo sapiens	80-83
33226337-5	2020	Additionally, we find that a remote Ibrutinib resistance mutation, T316A in the BTK SH2 domain, drives spurious BTK activity by destabilizing the compact autoinhibitory conformation of full-length BTK, shifting the conformational ensemble away from the autoinhibited form.	ibrutinib	36-45	Bruton tyrosine kinase	Homo sapiens	112-115
33226337-5	2020	Additionally, we find that a remote Ibrutinib resistance mutation, T316A in the BTK SH2 domain, drives spurious BTK activity by destabilizing the compact autoinhibitory conformation of full-length BTK, shifting the conformational ensemble away from the autoinhibited form.	ibrutinib	36-45	Bruton tyrosine kinase	Homo sapiens	112-115
32917401-1	2020	INTRODUCTION: Ibrutinib is a selective oral inhibitor of Bruton"s tyrosine kinase.	ibrutinib	14-23	Bruton tyrosine kinase	Homo sapiens	57-81
33658926-1	2020	Background: Ibrutinib is an oral covalent Bruton"s tyrosine kinase inhibitor that has been approved for chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia and some other B-cell malignancies.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	42-66
33067379-0	2020	Effect of Ibrutinib on the IFN Response of Chronic Lymphocytic Leukemia Cells.	ibrutinib	10-19	interferon alpha 1	Homo sapiens	27-30
33067379-1	2020	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has profound activity in chronic lymphocytic leukemia (CLL) but limited curative potential by itself.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
33067379-1	2020	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has profound activity in chronic lymphocytic leukemia (CLL) but limited curative potential by itself.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
33067379-3	2020	Ongoing activation of IFN receptors in patients on ibrutinib was suggested by the presence of type I and II IFN in blood together with the cycling behavior of IFN-stimulated gene (ISG) products when IFN signaling was blocked intermittently with the JAK inhibitor ruxolitinib.	ibrutinib	51-60	interferon alpha 1	Homo sapiens	22-25
33067379-3	2020	Ongoing activation of IFN receptors in patients on ibrutinib was suggested by the presence of type I and II IFN in blood together with the cycling behavior of IFN-stimulated gene (ISG) products when IFN signaling was blocked intermittently with the JAK inhibitor ruxolitinib.	ibrutinib	51-60	interferon alpha 1	Homo sapiens	108-111
33067379-3	2020	Ongoing activation of IFN receptors in patients on ibrutinib was suggested by the presence of type I and II IFN in blood together with the cycling behavior of IFN-stimulated gene (ISG) products when IFN signaling was blocked intermittently with the JAK inhibitor ruxolitinib.	ibrutinib	51-60	interferon alpha 1	Homo sapiens	108-111
33067379-5	2020	ISGs such as CXCL10 that require concomitant activation of NF-kappaB were decreased when this pathway was inhibited by ibrutinib.	ibrutinib	119-128	C-X-C motif chemokine ligand 10	Homo sapiens	13-19
33067379-5	2020	ISGs such as CXCL10 that require concomitant activation of NF-kappaB were decreased when this pathway was inhibited by ibrutinib.	ibrutinib	119-128	nuclear factor kappa B subunit 1	Homo sapiens	59-68
33067379-7	2020	Effects of IFN on survival remained intact as type I and II IFN-protected CLL cells from ibrutinib in vitro, which could be prevented by ruxolitinib and IFNR blocking Abs.	ibrutinib	89-98	interferon alpha 1	Homo sapiens	60-63
33067379-7	2020	Effects of IFN on survival remained intact as type I and II IFN-protected CLL cells from ibrutinib in vitro, which could be prevented by ruxolitinib and IFNR blocking Abs.	ibrutinib	89-98	interferon production regulator	Homo sapiens	153-157
32671454-0	2020	A case of "double hit" mantle cell lymphoma carrying CCND1 and MYC translocations relapsed/refractory to rituximab bendamustine cytarabine (R-BAC) and ibrutinib.	ibrutinib	151-160	cyclin D1	Homo sapiens	53-58
32671454-0	2020	A case of "double hit" mantle cell lymphoma carrying CCND1 and MYC translocations relapsed/refractory to rituximab bendamustine cytarabine (R-BAC) and ibrutinib.	ibrutinib	151-160	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	63-66
32876369-1	2020	Ibrutinib might improve the efficacy of anti-CD19 chimeric antigen receptor (CD19 CAR) T cell therapy in chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	CD19 molecule	Homo sapiens	45-49
32876369-1	2020	Ibrutinib might improve the efficacy of anti-CD19 chimeric antigen receptor (CD19 CAR) T cell therapy in chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	CD19 molecule	Homo sapiens	77-81
32876369-3	2020	In this study, we selected the CD19 CAR-T cells of a patient with lymphoma who failed in his CD19 CAR-T cell therapy and a dose of 8 mg/kg/day ibrutinib.	ibrutinib	143-152	CD19 molecule	Homo sapiens	31-35
32660904-0	2020	Complete Response of a Young Woman With MYD88WT Bing-Neel Syndrome on Ibrutinib Monotherapy Following a Single Cycle of B Hyper-CVAD/IT MTX.	ibrutinib	70-79	MYD88 innate immune signal transduction adaptor	Homo sapiens	40-45
33097837-7	2021	Although we found ibrutinib could inhibit the phosphorylation of ERK1/2 and DOCK2 induced by B-cell-receptor ligation, we found that this drug was unable to inhibit Wnt5a-induced, ROR1-dependent phosphorylation of ERK1/2 or DOCK2.	ibrutinib	18-27	mitogen-activated protein kinase 3	Mus musculus	65-71
32790083-1	2020	Ibrutinib is a Burton tyrosine kinase inhibitor (BTKi) approved for the treatment of several hematologic malignancies.	ibrutinib	0-9	inhibitor of Bruton tyrosine kinase	Homo sapiens	15-47
32790083-1	2020	Ibrutinib is a Burton tyrosine kinase inhibitor (BTKi) approved for the treatment of several hematologic malignancies.	ibrutinib	0-9	inhibitor of Bruton tyrosine kinase	Homo sapiens	49-53
32777360-0	2020	Ibrutinib, a Bruton"s tyrosine kinase inhibitor, a new risk factor for cryptococcosis.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-37
32777360-1	2020	PURPOSE: Invasive fungal diseases and especially Cryptococcus neoformans infections are increasingly reported in patients with hematological malignancies receiving ibrutinib, a Bruton"s tyrosine kinase inhibitor.	ibrutinib	164-173	Bruton tyrosine kinase	Homo sapiens	177-201
33154951-1	2020	The approval of BTK and PI3K inhibitors (ibrutinib, idelalisib) represents a revolution in the therapy of B cell malignancies such as chronic lymphocytic leukemia (CLL), mantle-cell lymphoma (MCL), diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), or Waldenstrom"s macroglobulinemia (WM).	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	16-19
33154951-3	2020	In ibrutinib treated patients, the most commonly described resistance-mechanism is a mutation in BTK itself, which prevents the covalent binding of ibrutinib, or a mutation in PLCG2, which acts to bypass the dependency on BTK at the BCR signalosome.	ibrutinib	3-12	Bruton tyrosine kinase	Homo sapiens	97-100
33154951-3	2020	In ibrutinib treated patients, the most commonly described resistance-mechanism is a mutation in BTK itself, which prevents the covalent binding of ibrutinib, or a mutation in PLCG2, which acts to bypass the dependency on BTK at the BCR signalosome.	ibrutinib	3-12	phospholipase C gamma 2	Homo sapiens	176-181
33154951-3	2020	In ibrutinib treated patients, the most commonly described resistance-mechanism is a mutation in BTK itself, which prevents the covalent binding of ibrutinib, or a mutation in PLCG2, which acts to bypass the dependency on BTK at the BCR signalosome.	ibrutinib	3-12	Bruton tyrosine kinase	Homo sapiens	222-225
33154951-3	2020	In ibrutinib treated patients, the most commonly described resistance-mechanism is a mutation in BTK itself, which prevents the covalent binding of ibrutinib, or a mutation in PLCG2, which acts to bypass the dependency on BTK at the BCR signalosome.	ibrutinib	148-157	Bruton tyrosine kinase	Homo sapiens	97-100
33154951-11	2020	Here we review the genetic and non-genetic mechanisms of resistance and adaptation to the first generation of BTK and PI3K inhibitors (ibrutinib and idelalisib, respectively), and discuss possible combinatorial therapeutic strategies to overcome resistance or to increase clinical efficacy.	ibrutinib	135-144	Bruton tyrosine kinase	Homo sapiens	110-113
33097837-7	2021	Although we found ibrutinib could inhibit the phosphorylation of ERK1/2 and DOCK2 induced by B-cell-receptor ligation, we found that this drug was unable to inhibit Wnt5a-induced, ROR1-dependent phosphorylation of ERK1/2 or DOCK2.	ibrutinib	18-27	dedicator of cyto-kinesis 2	Mus musculus	76-81
32894935-4	2020	Herein, we proposed a covalent inhibitor-based, one-step method for G protein-coupled receptor (GPCR) immobilization inspired by the covalent reaction between an epidermal growth factor receptor (EGFR)-tag and its inhibitor ibrutinib.	ibrutinib	224-233	epidermal growth factor receptor	Homo sapiens	162-194
32518952-6	2020	However, using ibrutinib in the first-line led to significantly higher healthcare costs (incremental cost of $612,700), resulting in an ICER of $2,350,041/QALY.	ibrutinib	15-24	cAMP responsive element modulator	Homo sapiens	136-140
32518952-8	2020	In a scenario analysis where ibrutinib was used in the second-line in the delayed ibrutinib arm, first-line ibrutinib had an incremental cost of $478,823, an incremental effectiveness of 0.05 QALYs, and an ICER of $9,810,360/QALY when compared to second-line use.	ibrutinib	29-38	cAMP responsive element modulator	Homo sapiens	206-210
33087831-9	2021	Interestingly, elevated CXCL13 plasma levels normalized during ibrutinib therapy, and increased in ibrutinib resistance patients.	ibrutinib	63-72	C-X-C motif chemokine ligand 13	Homo sapiens	24-30
33087831-9	2021	Interestingly, elevated CXCL13 plasma levels normalized during ibrutinib therapy, and increased in ibrutinib resistance patients.	ibrutinib	99-108	C-X-C motif chemokine ligand 13	Homo sapiens	24-30
32894935-4	2020	Herein, we proposed a covalent inhibitor-based, one-step method for G protein-coupled receptor (GPCR) immobilization inspired by the covalent reaction between an epidermal growth factor receptor (EGFR)-tag and its inhibitor ibrutinib.	ibrutinib	224-233	epidermal growth factor receptor	Homo sapiens	196-200
32833105-0	2020	LPL deletion is associated with poorer response to ibrutinib-based treatments and overall survival in TP53-deleted chronic lymphocytic leukemia.	ibrutinib	51-60	lipoprotein lipase	Homo sapiens	0-3
33214835-7	2020	Cotreatment of JH-X-119-01 with the BTK inhibitor ibrutinib resulted in synergistic killing effects in these systems.	ibrutinib	50-59	Bruton tyrosine kinase	Homo sapiens	36-39
33162993-7	2020	Ibrutinib, a Bruton tyrosine kinase (Btk) inhibitor, has recently been approved by the Food and Drug Administration (FDA) in the United States for the treatment of adult patients with cGvHD after failure of first-line of systemic therapy.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-35
33162993-7	2020	Ibrutinib, a Bruton tyrosine kinase (Btk) inhibitor, has recently been approved by the Food and Drug Administration (FDA) in the United States for the treatment of adult patients with cGvHD after failure of first-line of systemic therapy.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	37-40
33162995-1	2020	We previously reported the Bruton"s tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib improve outcomes in a mouse model of polymicrobial sepsis.	ibrutinib	69-78	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	27-51
33162995-1	2020	We previously reported the Bruton"s tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib improve outcomes in a mouse model of polymicrobial sepsis.	ibrutinib	69-78	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	53-56
33162995-6	2020	Importantly no further reduction in organ damage, cytokine production, or changes in plasma metabolites is seen in Xid mice treated with the BTK inhibitor ibrutinib, demonstrating that the protective effects of BTK inhibitors in polymicrobial sepsis are mediated solely by inhibition of BTK and not by off-target effects of this class of drugs.	ibrutinib	155-164	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	141-144
32833105-1	2020	Ibrutinib-based therapy represents a recent success in managing high-risk CLL patients with 17p/TP53 deletion.	ibrutinib	0-9	tumor protein p53	Homo sapiens	96-100
32833105-3	2020	Deletion of lipoprotein lipase (LPL) has been postulated as a potential evasion mechanism to ibrutinib-based therapy.	ibrutinib	93-102	lipoprotein lipase	Homo sapiens	12-30
32833105-3	2020	Deletion of lipoprotein lipase (LPL) has been postulated as a potential evasion mechanism to ibrutinib-based therapy.	ibrutinib	93-102	lipoprotein lipase	Homo sapiens	32-35
32833105-8	2020	The overall response to ibrutinib-based therapy was 57%, including 37% complete remission (CR) and 20% partial remission (PR) in patients with LPL-del versus 90% (56% CR and 34% PR) in patients with LPL-nml (p < 0.001).	ibrutinib	24-33	lipoprotein lipase	Homo sapiens	143-146
32833105-8	2020	The overall response to ibrutinib-based therapy was 57%, including 37% complete remission (CR) and 20% partial remission (PR) in patients with LPL-del versus 90% (56% CR and 34% PR) in patients with LPL-nml (p < 0.001).	ibrutinib	24-33	lipoprotein lipase	Homo sapiens	199-202
32833105-10	2020	In summary, the data presented establish an association between LPL deletion, resistance to ibrutinib-based therapy, and poorer overall survival in TP53-deleted CLL patients.	ibrutinib	92-101	lipoprotein lipase	Homo sapiens	64-67
32833105-10	2020	In summary, the data presented establish an association between LPL deletion, resistance to ibrutinib-based therapy, and poorer overall survival in TP53-deleted CLL patients.	ibrutinib	92-101	tumor protein p53	Homo sapiens	148-152
32608058-5	2020	Treatment of mice fed HFD with ibrutinib inhibited the activation of BTK and reduced monocyte/macrophage recruitment to the liver, adipose tissue and kidney.	ibrutinib	31-40	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	69-72
32608058-7	2020	As a result, ibrutinib treated mice fed HFD had improved glycaemic control through restored signalling by the IRS-1/Akt/GSK-3beta pathway; protecting mice against the development of hepatosteatosis and proteinuria.	ibrutinib	13-22	insulin receptor substrate 1	Mus musculus	110-115
32608058-7	2020	As a result, ibrutinib treated mice fed HFD had improved glycaemic control through restored signalling by the IRS-1/Akt/GSK-3beta pathway; protecting mice against the development of hepatosteatosis and proteinuria.	ibrutinib	13-22	thymoma viral proto-oncogene 1	Mus musculus	116-119
32608058-7	2020	As a result, ibrutinib treated mice fed HFD had improved glycaemic control through restored signalling by the IRS-1/Akt/GSK-3beta pathway; protecting mice against the development of hepatosteatosis and proteinuria.	ibrutinib	13-22	glycogen synthase kinase 3 alpha	Mus musculus	120-129
32608058-8	2020	We show that inhibition of BTK reduces activation of NF-kappaB and the NLRP3 inflammasome specifically in primary murine and human macrophages; which are the primary target of ibrutinib in vivo in the setting of metabolic inflammation.	ibrutinib	176-185	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	27-30
32608058-8	2020	We show that inhibition of BTK reduces activation of NF-kappaB and the NLRP3 inflammasome specifically in primary murine and human macrophages; which are the primary target of ibrutinib in vivo in the setting of metabolic inflammation.	ibrutinib	176-185	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	53-62
32608058-8	2020	We show that inhibition of BTK reduces activation of NF-kappaB and the NLRP3 inflammasome specifically in primary murine and human macrophages; which are the primary target of ibrutinib in vivo in the setting of metabolic inflammation.	ibrutinib	176-185	NLR family, pyrin domain containing 3	Mus musculus	71-76
32861289-5	2020	We review preliminary safety and efficacy data of 2 pivotal trials investigating the use of CD19-targeted CAR-T cells for R/R MCL after ibrutinib failure and discuss potential timing of these approaches.	ibrutinib	136-145	CD19 molecule	Homo sapiens	92-96
32847720-3	2020	In addition to the reports on neratinib and pyrotinib, osimertinib, alflutinib, AST5902, and ibrutinib were confirmed to covalently bind to the Lys-190 of human serum albumin (HSA).	ibrutinib	93-102	albumin	Homo sapiens	161-174
32893700-4	2020	AREAS COVERED: Anti-CD22 recombinant immunotoxin Moxetumomab Pasudotox (Moxe), CD20 Mabs rituximab and obinutuzumab, BRAF/MEK inhibitors vemurafenib and dabrafenib-trametinib, and Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib have been tested for HCL.	ibrutinib	221-230	CD22 molecule	Homo sapiens	20-24
33054082-2	2020	Exploiting these vulnerabilities has been shown to be an effective anti-tumor strategy as demonstrated for example by the Bruton"s tyrosine kinase (BTK) inhibitor, ibrutinib, for treatment of various blood cancers.	ibrutinib	164-173	Bruton tyrosine kinase	Homo sapiens	122-146
33054082-2	2020	Exploiting these vulnerabilities has been shown to be an effective anti-tumor strategy as demonstrated for example by the Bruton"s tyrosine kinase (BTK) inhibitor, ibrutinib, for treatment of various blood cancers.	ibrutinib	164-173	Bruton tyrosine kinase	Homo sapiens	148-151
32880204-2	2020	Limited real-word evidence is available on the outcomes of ibrutinib use among previously untreated patients in the U.S. Veterans Health Administration (VHA) population diagnosed with CLL/SLL.	ibrutinib	59-68	solute carrier family 35 member B2	Homo sapiens	188-191
31965420-4	2020	The efficacy of ibrutinib, a B cell receptor inhibitor, for B-PLL with the TP53 abnormality as second-line therapy was recently demonstrated.	ibrutinib	16-25	tumor protein p53	Homo sapiens	75-79
31965420-5	2020	We herein report that low-dose ibrutinib as upfront therapy induced a complete response in a B-PLL patient with the TP53 abnormality, whose condition has since remained stable with no recurrence for 12 months.	ibrutinib	31-40	tumor protein p53	Homo sapiens	116-120
32880204-3	2020	OBJECTIVES: To (a) evaluate time to next treatment (TTNT) among U.S. veterans with CLL/SLL who initiated ibrutinib versus chemoimmunotherapy (CIT) in first line (1L) and 1L ibrutinib versus ibrutinib in later lines (2L+) and (b) compare health care resource utilization (HRU) and costs between the 1L ibrutinib and CIT cohorts.	ibrutinib	105-114	solute carrier family 35 member B2	Homo sapiens	87-90
32880204-11	2020	CONCLUSIONS: These findings demonstrate that among U.S. veterans with CLL/SLL, 1L ibrutinib use was associated with significantly longer TTNT versus that of 1L CIT.	ibrutinib	82-91	solute carrier family 35 member B2	Homo sapiens	74-77
32508208-2	2020	The Bruton tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib mark major breakthroughs in the treatment of CLL, however many patients require long-term therapy with these agents.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	4-26
32511880-1	2020	BACKGROUND: Therapy with irrevesible Bruton"s tyrosine kinase inhibitor ibrutinib in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) is associated with bleeding.	ibrutinib	72-81	Bruton tyrosine kinase	Homo sapiens	37-61
32306816-1	2020	Ibrutinib is a BTK/ITK inhibitor with efficacy for the treatment of various lymphoid cancers, including CLL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	15-18
32306816-1	2020	Ibrutinib is a BTK/ITK inhibitor with efficacy for the treatment of various lymphoid cancers, including CLL.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	19-22
32508208-2	2020	The Bruton tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib mark major breakthroughs in the treatment of CLL, however many patients require long-term therapy with these agents.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	28-31
32306816-4	2020	We found that ibrutinib reduces the production of reactive oxygen species (ROS) and bacteria killing capacity, and slightly impairs neutrophil extracellular traps (NETs) production without affecting bacteria-uptake and CD62L-downregulation induced by fMLP or aggregated IgG.	ibrutinib	14-23	formyl peptide receptor 1	Homo sapiens	251-255
32684632-7	2020	Subsequently, we identified BTK as a main downstream mediator and targeting the Bcr-Abl-FcgammaRIIb-BTK axis in primary CML CD34+ cells using ibrutinib, in combination with standard TKI therapy, significantly increased apoptosis in quiescent CML stem cells thereby contributing to the eradication of LSCs.. As a potential curative therapeutic approach, we therefore suggest combining Bcr-Abl TKI therapy along with BTK inhibition.	ibrutinib	142-151	Bruton tyrosine kinase	Homo sapiens	28-31
32306816-5	2020	In addition, ibrutinib reduces gammadelta T cell activation and CD107a degranulation induced by phosphoantigens or anti-CD3.	ibrutinib	13-22	lysosomal associated membrane protein 1	Homo sapiens	64-70
32684632-7	2020	Subsequently, we identified BTK as a main downstream mediator and targeting the Bcr-Abl-FcgammaRIIb-BTK axis in primary CML CD34+ cells using ibrutinib, in combination with standard TKI therapy, significantly increased apoptosis in quiescent CML stem cells thereby contributing to the eradication of LSCs.. As a potential curative therapeutic approach, we therefore suggest combining Bcr-Abl TKI therapy along with BTK inhibition.	ibrutinib	142-151	Bruton tyrosine kinase	Homo sapiens	100-103
32684632-7	2020	Subsequently, we identified BTK as a main downstream mediator and targeting the Bcr-Abl-FcgammaRIIb-BTK axis in primary CML CD34+ cells using ibrutinib, in combination with standard TKI therapy, significantly increased apoptosis in quiescent CML stem cells thereby contributing to the eradication of LSCs.. As a potential curative therapeutic approach, we therefore suggest combining Bcr-Abl TKI therapy along with BTK inhibition.	ibrutinib	142-151	CD34 molecule	Homo sapiens	124-128
32684632-7	2020	Subsequently, we identified BTK as a main downstream mediator and targeting the Bcr-Abl-FcgammaRIIb-BTK axis in primary CML CD34+ cells using ibrutinib, in combination with standard TKI therapy, significantly increased apoptosis in quiescent CML stem cells thereby contributing to the eradication of LSCs.. As a potential curative therapeutic approach, we therefore suggest combining Bcr-Abl TKI therapy along with BTK inhibition.	ibrutinib	142-151	ABL proto-oncogene 1, non-receptor tyrosine kinase	Homo sapiens	80-87
32684632-7	2020	Subsequently, we identified BTK as a main downstream mediator and targeting the Bcr-Abl-FcgammaRIIb-BTK axis in primary CML CD34+ cells using ibrutinib, in combination with standard TKI therapy, significantly increased apoptosis in quiescent CML stem cells thereby contributing to the eradication of LSCs.. As a potential curative therapeutic approach, we therefore suggest combining Bcr-Abl TKI therapy along with BTK inhibition.	ibrutinib	142-151	Bruton tyrosine kinase	Homo sapiens	100-103
32911375-4	2020	Ibrutinib significantly decreased pathologically high circulating B cells, regulatory T cells, effector/memory CD4+ and CD8+ T cells (including exhausted and chronically activated T cells), natural killer (NK) T cells, and myeloid-derived suppressor cells; preserved naive T cells and NK cells; and increased circulating classical monocytes.	ibrutinib	0-9	CD4 molecule	Homo sapiens	111-114
32945596-1	2020	Ibrutinib may inhibit intestinal CYP3A4 and induce CYP2B6 and/or CYP3A.	ibrutinib	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	33-39
32911375-4	2020	Ibrutinib significantly decreased pathologically high circulating B cells, regulatory T cells, effector/memory CD4+ and CD8+ T cells (including exhausted and chronically activated T cells), natural killer (NK) T cells, and myeloid-derived suppressor cells; preserved naive T cells and NK cells; and increased circulating classical monocytes.	ibrutinib	0-9	CD8a molecule	Homo sapiens	120-123
32945596-1	2020	Ibrutinib may inhibit intestinal CYP3A4 and induce CYP2B6 and/or CYP3A.	ibrutinib	0-9	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	51-57
32945596-1	2020	Ibrutinib may inhibit intestinal CYP3A4 and induce CYP2B6 and/or CYP3A.	ibrutinib	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	33-38
32945596-3	2020	This phase I study evaluated the effect of ibrutinib on the pharmacokinetics of the CYP2B6 substrate bupropion, CYP3A substrate midazolam, and OCs ethinylestradiol (EE) and levonorgestrel (LN).	ibrutinib	43-52	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	84-90
32945596-8	2020	On day 8, the GMR for midazolam exposure with ibrutinib coadministration was <= 20% lower than the reference, indicating lack of intestinal CYP3A4 inhibition.	ibrutinib	46-55	colony stimulating factor 2 receptor subunit alpha	Homo sapiens	14-17
32563910-9	2020	Ibrutinib was biologically active, since hCD19+ cells harvested from ibrutinib treated mice had no detectable levels of phospho-BTK at tyrosine 223 (pBTK Y223), whereas pBTK Y223 was still detectable in placebo treated cases.	ibrutinib	0-9	CD19 molecule	Homo sapiens	41-46
33005100-3	2020	Ibrutinib, the first generation of BTK inhibitor, has shown excellent antitumor activity in both indolent and aggressive B-cell lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	35-38
32563910-1	2020	AIM: The Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib (PCI-32765) is effective in patients with multiple myeloma, non-Hodgkin lymphoma and chronic lymphoblastic leukemia.	ibrutinib	50-59	Bruton tyrosine kinase	Homo sapiens	9-33
32563910-1	2020	AIM: The Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib (PCI-32765) is effective in patients with multiple myeloma, non-Hodgkin lymphoma and chronic lymphoblastic leukemia.	ibrutinib	50-59	Bruton tyrosine kinase	Homo sapiens	35-38
32563910-1	2020	AIM: The Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib (PCI-32765) is effective in patients with multiple myeloma, non-Hodgkin lymphoma and chronic lymphoblastic leukemia.	ibrutinib	61-70	Bruton tyrosine kinase	Homo sapiens	9-33
32563910-1	2020	AIM: The Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib (PCI-32765) is effective in patients with multiple myeloma, non-Hodgkin lymphoma and chronic lymphoblastic leukemia.	ibrutinib	61-70	Bruton tyrosine kinase	Homo sapiens	35-38
32563910-2	2020	We previously showed that primary cells of children with TCF3-PBX1 positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) express BTK and are sensitive to ibrutinib in vitro.	ibrutinib	165-174	transcription factor 3	Homo sapiens	57-61
32563910-2	2020	We previously showed that primary cells of children with TCF3-PBX1 positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) express BTK and are sensitive to ibrutinib in vitro.	ibrutinib	165-174	PBX homeobox 1	Homo sapiens	62-66
32563910-4	2020	METHODS: Immunocompromised NSG mice were engrafted with a luciferase-positive TCF3-PBX1 leukemic cell line or primary leukemic cells and treated with ibrutinib or placebo.	ibrutinib	150-159	transcription factor 3	Mus musculus	78-82
32563910-4	2020	METHODS: Immunocompromised NSG mice were engrafted with a luciferase-positive TCF3-PBX1 leukemic cell line or primary leukemic cells and treated with ibrutinib or placebo.	ibrutinib	150-159	pre B cell leukemia homeobox 1	Mus musculus	83-87
32563910-6	2020	RESULTS: Treatment with ibrutinib of mice engrafted with a TCF3-PBX1 cell line, TCF3-PBX1 positive or TCF3-PBX1 negative primary leukemic cells did not result in prolonged life span compared to placebo treated mice.	ibrutinib	24-33	transcription factor 3	Mus musculus	59-63
32563910-6	2020	RESULTS: Treatment with ibrutinib of mice engrafted with a TCF3-PBX1 cell line, TCF3-PBX1 positive or TCF3-PBX1 negative primary leukemic cells did not result in prolonged life span compared to placebo treated mice.	ibrutinib	24-33	pre B cell leukemia homeobox 1	Mus musculus	64-68
32563910-6	2020	RESULTS: Treatment with ibrutinib of mice engrafted with a TCF3-PBX1 cell line, TCF3-PBX1 positive or TCF3-PBX1 negative primary leukemic cells did not result in prolonged life span compared to placebo treated mice.	ibrutinib	24-33	transcription factor 3	Mus musculus	80-84
32563910-6	2020	RESULTS: Treatment with ibrutinib of mice engrafted with a TCF3-PBX1 cell line, TCF3-PBX1 positive or TCF3-PBX1 negative primary leukemic cells did not result in prolonged life span compared to placebo treated mice.	ibrutinib	24-33	pre B cell leukemia homeobox 1	Mus musculus	85-89
32563910-6	2020	RESULTS: Treatment with ibrutinib of mice engrafted with a TCF3-PBX1 cell line, TCF3-PBX1 positive or TCF3-PBX1 negative primary leukemic cells did not result in prolonged life span compared to placebo treated mice.	ibrutinib	24-33	transcription factor 3	Mus musculus	80-84
32563910-6	2020	RESULTS: Treatment with ibrutinib of mice engrafted with a TCF3-PBX1 cell line, TCF3-PBX1 positive or TCF3-PBX1 negative primary leukemic cells did not result in prolonged life span compared to placebo treated mice.	ibrutinib	24-33	pre B cell leukemia homeobox 1	Mus musculus	85-89
32994268-2	2020	Ibrutinib, a tyrosine kinase inhibitor, is the treatment of choice on relapse or p53-dysfunction.	ibrutinib	0-9	tumor protein p53	Homo sapiens	81-84
33043320-1	2020	Ibrutinib, a known Burton"s tyrosine kinase (BTK) and interleukin-2 inducible T-cell kinase (ITK) inhibitor, is used for the treatment of B-cell disorders (chronic lymphocytic leukemia [CLL] and various other lymphomas) and chronic graft versus host disease following allogeneic hematopoietic cell transplantation.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	54-91
32977449-3	2020	Here we report that the TNF family member B-cell activating factor (BAFF) mediates resistance of CLL cells to idelalisib, ibrutinib and venetoclax by sustaining survival and preventing apoptosis of the malignant B cells as revealed by analysis of cellular ATP levels and mitochondrial membrane integrity as well as caspase activation, respectively.	ibrutinib	122-131	TNF superfamily member 13b	Homo sapiens	68-72
32926124-3	2020	Targeting BTK with ibrutinib, an inhibitor, provides a therapeutic approach for this subtype of DLBCL.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	10-13
32926124-7	2020	Reduced levels of BTK and enhanced phosphatidylinositol 3-kinase (PI3K)/AKT signaling were hallmarks of these ibrutinib-resistant cells.	ibrutinib	110-119	Bruton tyrosine kinase	Homo sapiens	18-21
32926124-7	2020	Reduced levels of BTK and enhanced phosphatidylinositol 3-kinase (PI3K)/AKT signaling were hallmarks of these ibrutinib-resistant cells.	ibrutinib	110-119	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta	Homo sapiens	35-64
32926124-7	2020	Reduced levels of BTK and enhanced phosphatidylinositol 3-kinase (PI3K)/AKT signaling were hallmarks of these ibrutinib-resistant cells.	ibrutinib	110-119	AKT serine/threonine kinase 1	Homo sapiens	72-75
32926124-8	2020	Upregulation of PI3K-beta expression was demonstrated to drive resistance in ibrutinib-resistant cells, and resistance was reversed by the blocking activity of PI3K-beta/delta.	ibrutinib	77-86	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta	Homo sapiens	16-25
32926124-8	2020	Upregulation of PI3K-beta expression was demonstrated to drive resistance in ibrutinib-resistant cells, and resistance was reversed by the blocking activity of PI3K-beta/delta.	ibrutinib	77-86	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta	Homo sapiens	160-169
32926124-9	2020	Treatment with the selective PI3K-beta/delta dual inhibitor KA2237 reduced both tumorigenic properties and survival-based PI3K/AKT/mTOR signaling of these ibrutinib-resistant cells.	ibrutinib	155-164	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta	Homo sapiens	29-38
32926124-9	2020	Treatment with the selective PI3K-beta/delta dual inhibitor KA2237 reduced both tumorigenic properties and survival-based PI3K/AKT/mTOR signaling of these ibrutinib-resistant cells.	ibrutinib	155-164	AKT serine/threonine kinase 1	Homo sapiens	127-130
32926124-9	2020	Treatment with the selective PI3K-beta/delta dual inhibitor KA2237 reduced both tumorigenic properties and survival-based PI3K/AKT/mTOR signaling of these ibrutinib-resistant cells.	ibrutinib	155-164	mechanistic target of rapamycin kinase	Homo sapiens	131-135
32926124-11	2020	This study elucidates the compensatory upregulated PI3K/AKT axis that emerges in ibrutinib-resistant cells.	ibrutinib	81-90	AKT serine/threonine kinase 1	Homo sapiens	56-59
33043320-1	2020	Ibrutinib, a known Burton"s tyrosine kinase (BTK) and interleukin-2 inducible T-cell kinase (ITK) inhibitor, is used for the treatment of B-cell disorders (chronic lymphocytic leukemia [CLL] and various other lymphomas) and chronic graft versus host disease following allogeneic hematopoietic cell transplantation.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	19-43
33043320-1	2020	Ibrutinib, a known Burton"s tyrosine kinase (BTK) and interleukin-2 inducible T-cell kinase (ITK) inhibitor, is used for the treatment of B-cell disorders (chronic lymphocytic leukemia [CLL] and various other lymphomas) and chronic graft versus host disease following allogeneic hematopoietic cell transplantation.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	45-48
33043320-1	2020	Ibrutinib, a known Burton"s tyrosine kinase (BTK) and interleukin-2 inducible T-cell kinase (ITK) inhibitor, is used for the treatment of B-cell disorders (chronic lymphocytic leukemia [CLL] and various other lymphomas) and chronic graft versus host disease following allogeneic hematopoietic cell transplantation.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	93-96
33479617-4	2020	As a result, pharma and academic efforts have succeeded in progressing several pyrazolo[3,4-d]pyrimidines to clinical trials, including the BTK inhibitor ibrutinib, which has been approved for the treatment of several B-cell cancers.	ibrutinib	154-163	Bruton tyrosine kinase	Homo sapiens	140-143
32963499-0	2020	The Ibr-7 derivative of ibrutinib radiosensitizes pancreatic cancer cells by downregulating p-EGFR.	ibrutinib	24-33	epidermal growth factor receptor	Homo sapiens	94-98
32855753-1	2020	Background: Ibrutinib is a Bruton"s tyrosine kinase inhibitor that has shown to be a superior choice in the treatment of chronic lymphocytic leukemia (CLL) and a simple, oral alternative to other chemoimmunotherapies.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	27-51
32328976-13	2020	Observed ibrutinib exposure is significantly higher in patients carrying one copy of the cytochrome P450 3A4*22 variant (1167 ng.h/mL vs 743 ng.h/mL, respectively, p = 0.024).	ibrutinib	9-18	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	89-108
32603202-9	2020	EXPERT OPINION: The evidence for the use of Ibrutinib as a treatment option for relapsed/refractory WM is compelling in MYD88 mutated WM with the response and survival rates potentially better than conventional salvage chemoimmunotherapy.	ibrutinib	44-53	MYD88 innate immune signal transduction adaptor	Homo sapiens	120-125
33093256-3	2020	In this article, we describe two patients with CLL who developed an IFI during treatment with the BTK inhibitor ibrutinib.	ibrutinib	112-121	Bruton tyrosine kinase	Homo sapiens	98-101
32094466-2	2020	Using an ex vivo functional screening assay, we identified that the combination of the BTK inhibitor ibrutinib and BCL2 inhibitor venetoclax (IBR + VEN), currently in clinical trials for chronic lymphocytic leukemia (CLL), demonstrated enhanced efficacy on primary AML patient specimens, AML cell lines, and in a mouse xenograft model of AML.	ibrutinib	101-110	Bruton tyrosine kinase	Homo sapiens	87-90
32712432-0	2020	Antihistamines are synergistic with Bruton"s tyrosine kinase inhibiter ibrutinib mediated by lysosome disruption in chronic lymphocytic leukemia (CLL) cells.	ibrutinib	71-80	Bruton tyrosine kinase	Homo sapiens	36-60
32712432-7	2020	Moreover, the synergy between clemastine and ibrutinib was associated with the induction of reactive oxygen species (ROS), loss of mitochondrial membrane potential and decreased Mcl-1 expression leading to apoptosis.	ibrutinib	45-54	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	178-183
32319217-0	2020	SWATH-Proteomics of Ibrutinib"s Action in Myeloid Leukemia Initiating Mutated G-CSFR Signaling.	ibrutinib	20-29	colony stimulating factor 3 receptor (granulocyte)	Mus musculus	78-84
32093809-5	2020	BTK inhibitor ibrutinib combined with BCL-2 inhibitors showed synergistic antitumor effect in DLBCL with mean expression of BCL-2 and myeloid cell leukemia-1 (MCL-1) through upregulating the expression level of BIM and modulating MCL-1 and p-Akt expression.	ibrutinib	14-23	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	0-3
32093809-5	2020	BTK inhibitor ibrutinib combined with BCL-2 inhibitors showed synergistic antitumor effect in DLBCL with mean expression of BCL-2 and myeloid cell leukemia-1 (MCL-1) through upregulating the expression level of BIM and modulating MCL-1 and p-Akt expression.	ibrutinib	14-23	B cell leukemia/lymphoma 2	Mus musculus	124-129
32093809-5	2020	BTK inhibitor ibrutinib combined with BCL-2 inhibitors showed synergistic antitumor effect in DLBCL with mean expression of BCL-2 and myeloid cell leukemia-1 (MCL-1) through upregulating the expression level of BIM and modulating MCL-1 and p-Akt expression.	ibrutinib	14-23	myeloid cell leukemia sequence 1	Mus musculus	134-157
32093809-5	2020	BTK inhibitor ibrutinib combined with BCL-2 inhibitors showed synergistic antitumor effect in DLBCL with mean expression of BCL-2 and myeloid cell leukemia-1 (MCL-1) through upregulating the expression level of BIM and modulating MCL-1 and p-Akt expression.	ibrutinib	14-23	myeloid cell leukemia sequence 1	Mus musculus	159-164
32093809-5	2020	BTK inhibitor ibrutinib combined with BCL-2 inhibitors showed synergistic antitumor effect in DLBCL with mean expression of BCL-2 and myeloid cell leukemia-1 (MCL-1) through upregulating the expression level of BIM and modulating MCL-1 and p-Akt expression.	ibrutinib	14-23	myeloid cell leukemia sequence 1	Mus musculus	230-235
32319217-1	2020	PURPOSE: To evaluate cellular protein changes in response to treatment with an approved drug, ibrutinib, in cells expressing normal or mutated Granulocyte-Colony Stimulating Factor Receptor (G-CSFR).	ibrutinib	94-103	colony stimulating factor 3 receptor (granulocyte)	Mus musculus	143-189
32319217-1	2020	PURPOSE: To evaluate cellular protein changes in response to treatment with an approved drug, ibrutinib, in cells expressing normal or mutated Granulocyte-Colony Stimulating Factor Receptor (G-CSFR).	ibrutinib	94-103	colony stimulating factor 3 receptor (granulocyte)	Mus musculus	191-197
32319217-3	2020	Previous studies showed the efficacy of ibrutinib (a Bruton"s tyrosine kinase inhibitor) in mutated G-CSFR leukemia models but did not addressed broader signaling mechanisms.	ibrutinib	40-49	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	53-77
32319217-3	2020	Previous studies showed the efficacy of ibrutinib (a Bruton"s tyrosine kinase inhibitor) in mutated G-CSFR leukemia models but did not addressed broader signaling mechanisms.	ibrutinib	40-49	colony stimulating factor 3 receptor (granulocyte)	Mus musculus	100-106
32983178-12	2020	Reduction of TNF-alpha secretion and phagocytosis are detected in monocytes isolated from CLL patients during ibrutinib therapy.	ibrutinib	110-119	tumor necrosis factor	Homo sapiens	13-22
32855274-7	2021	Moreover enhanced osteoclastogenesis, induced by CLL-cm, was significantly reduced by treating cultures with the anti-TNFalpha moAb Infliximab; an analogous effect was observed by the use of the BTK inhibitor Ibrutinib.	ibrutinib	209-218	tumor necrosis factor	Homo sapiens	118-126
32859260-4	2020	Ibrutinib inhibits the Bruton tyrosine kinase and thereby B-cell activity.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	23-45
32855274-7	2021	Moreover enhanced osteoclastogenesis, induced by CLL-cm, was significantly reduced by treating cultures with the anti-TNFalpha moAb Infliximab; an analogous effect was observed by the use of the BTK inhibitor Ibrutinib.	ibrutinib	209-218	Bruton tyrosine kinase	Homo sapiens	195-198
32864130-10	2020	CD79B and PIM1 mutations indicated a better response to inhibitors of BTK (ibrutinib) and pan-PIM kinase (AZD 1208) through repressing activated oncogenic signaling.	ibrutinib	75-84	CD79b molecule	Homo sapiens	0-5
32864130-10	2020	CD79B and PIM1 mutations indicated a better response to inhibitors of BTK (ibrutinib) and pan-PIM kinase (AZD 1208) through repressing activated oncogenic signaling.	ibrutinib	75-84	Pim-1 proto-oncogene, serine/threonine kinase	Homo sapiens	10-14
32864130-10	2020	CD79B and PIM1 mutations indicated a better response to inhibitors of BTK (ibrutinib) and pan-PIM kinase (AZD 1208) through repressing activated oncogenic signaling.	ibrutinib	75-84	Bruton tyrosine kinase	Homo sapiens	70-73
32824276-0	2020	Macrophage-Mediated Antibody Dependent Effector Function in Aggressive B-Cell Lymphoma Treatment is Enhanced by Ibrutinib via Inhibition of JAK2.	ibrutinib	112-121	Janus kinase 2	Homo sapiens	140-144
32984343-3	2020	Previous, we uncovered that the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is a potent reversal agent to overcomes paclitaxel resistance in ABCB1-overexpressing cells and tumors.	ibrutinib	73-82	Bruton tyrosine kinase	Homo sapiens	32-56
32984343-3	2020	Previous, we uncovered that the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is a potent reversal agent to overcomes paclitaxel resistance in ABCB1-overexpressing cells and tumors.	ibrutinib	73-82	Bruton tyrosine kinase	Homo sapiens	58-61
32984343-3	2020	Previous, we uncovered that the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is a potent reversal agent to overcomes paclitaxel resistance in ABCB1-overexpressing cells and tumors.	ibrutinib	73-82	ATP binding cassette subfamily B member 1	Homo sapiens	148-153
32824276-1	2020	Targeted inhibition of Bruton"s Tyrosine Kinase (BTK) with ibrutinib and other agents has become important treatment options in chronic lymphocytic leukemia, Waldenstrom"s Macroglobulinemia, Mantle cell lymphoma, and non-GCB DLBCL.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	23-47
32824276-1	2020	Targeted inhibition of Bruton"s Tyrosine Kinase (BTK) with ibrutinib and other agents has become important treatment options in chronic lymphocytic leukemia, Waldenstrom"s Macroglobulinemia, Mantle cell lymphoma, and non-GCB DLBCL.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	49-52
32824276-5	2020	Kinase activity profiling under BTK inhibition identified significant loss of Janus Kinase 2 (JAK2) only under ibrutinib treatment.	ibrutinib	111-120	Bruton tyrosine kinase	Homo sapiens	32-35
32824276-5	2020	Kinase activity profiling under BTK inhibition identified significant loss of Janus Kinase 2 (JAK2) only under ibrutinib treatment.	ibrutinib	111-120	Janus kinase 2	Homo sapiens	78-92
32824276-5	2020	Kinase activity profiling under BTK inhibition identified significant loss of Janus Kinase 2 (JAK2) only under ibrutinib treatment.	ibrutinib	111-120	Janus kinase 2	Homo sapiens	94-98
32447207-0	2020	The effect of ibrutinib on radiosensitivity in pancreatic cancer cells by targeting EGFR/AKT/mTOR signaling pathway.	ibrutinib	14-23	egfr	None	84-88
32447207-0	2020	The effect of ibrutinib on radiosensitivity in pancreatic cancer cells by targeting EGFR/AKT/mTOR signaling pathway.	ibrutinib	14-23	akt	None	89-92
32447207-0	2020	The effect of ibrutinib on radiosensitivity in pancreatic cancer cells by targeting EGFR/AKT/mTOR signaling pathway.	ibrutinib	14-23	mtor	None	93-97
32447207-12	2020	Further investigations revealed that ibrutinib decreased the phosphorylation of EGFR, then reversed the upregulation of p-AKT and downstream genes by radiation.	ibrutinib	37-46	egfr	None	80-84
32447207-12	2020	Further investigations revealed that ibrutinib decreased the phosphorylation of EGFR, then reversed the upregulation of p-AKT and downstream genes by radiation.	ibrutinib	37-46	akt	None	122-125
32209572-1	2020	PURPOSE: The safety and efficacy of ibrutinib, a once-daily Bruton"s tyrosine kinase inhibitor, in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was demonstrated in this phase 1b/2 study.	ibrutinib	36-45	solute carrier family 35 member B2	Homo sapiens	160-163
32580942-1	2020	Bruton"s tyrosine kinase inhibitor ibrutinib is effective in treating chronic lymphocytic leukemia (CLL).	ibrutinib	35-44	Bruton tyrosine kinase	Homo sapiens	0-24
32580942-4	2020	Using [68Ga]Pentixafor-PET/MRI (positron emission tomography/magnetic resonance imaging) for in vivo CXCR4 visualization, we here provide images of topical changes of CLL cells upon ibrutinib treatment.	ibrutinib	182-191	C-X-C motif chemokine receptor 4	Homo sapiens	101-106
32592909-2	2020	Targeted drugs already changed the clinical practice in treatment of leukemias, such as imatinib (BCR/ABL inhibitor) in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL), ibrutinib (Bruton"s tyrosine kinase inhibitor) in chronic lymphocytic leukemia (CLL), venetoclax (BCL2 inhibitor) in CLL and acute myeloid leukemia (AML) or midostaurin (FLT3 inhibitor) in AML.	ibrutinib	191-200	Bruton tyrosine kinase	Homo sapiens	202-226
32592909-2	2020	Targeted drugs already changed the clinical practice in treatment of leukemias, such as imatinib (BCR/ABL inhibitor) in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL), ibrutinib (Bruton"s tyrosine kinase inhibitor) in chronic lymphocytic leukemia (CLL), venetoclax (BCL2 inhibitor) in CLL and acute myeloid leukemia (AML) or midostaurin (FLT3 inhibitor) in AML.	ibrutinib	191-200	BCL2 apoptosis regulator	Homo sapiens	289-293
32592909-2	2020	Targeted drugs already changed the clinical practice in treatment of leukemias, such as imatinib (BCR/ABL inhibitor) in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL), ibrutinib (Bruton"s tyrosine kinase inhibitor) in chronic lymphocytic leukemia (CLL), venetoclax (BCL2 inhibitor) in CLL and acute myeloid leukemia (AML) or midostaurin (FLT3 inhibitor) in AML.	ibrutinib	191-200	fms related receptor tyrosine kinase 3	Homo sapiens	361-365
32209572-13	2020	CONCLUSIONS: With up to 8 years of follow-up, sustained responses and long-term tolerability of single-agent ibrutinib were observed with treatment of first-line or relapsed/refractory CLL/SLL, including high-risk CLL/SLL.	ibrutinib	109-118	solute carrier family 35 member B2	Homo sapiens	189-192
32209572-13	2020	CONCLUSIONS: With up to 8 years of follow-up, sustained responses and long-term tolerability of single-agent ibrutinib were observed with treatment of first-line or relapsed/refractory CLL/SLL, including high-risk CLL/SLL.	ibrutinib	109-118	solute carrier family 35 member B2	Homo sapiens	218-221
32378970-9	2020	Patients who relapse within 5 years are offered therapy with a novel agent that may include the BRAF inhibitor vemurafenib, alone or in combination with rituximab, dabrafenib in combination with trametinib, the BTK inhibitor ibrutinib, or moxetumomab pasudotox.	ibrutinib	225-234	Bruton tyrosine kinase	Homo sapiens	211-214
32791549-7	2020	Patients with the high-risk parameters deletion 17p or TP53mutation are known to poorly respond to chemo(immuno)therapy and should receive either ibrutinib or venetoclax/obinutuzumab.Thus, a choice has to be made between a continuous monotherapy with ibrutinib or a time-limited combination with either venetoclax/obinutuzumab (12 months) or chemoimmunotherapy (usually 6 months).	ibrutinib	146-155	tumor protein p53	Homo sapiens	55-59
32791549-7	2020	Patients with the high-risk parameters deletion 17p or TP53mutation are known to poorly respond to chemo(immuno)therapy and should receive either ibrutinib or venetoclax/obinutuzumab.Thus, a choice has to be made between a continuous monotherapy with ibrutinib or a time-limited combination with either venetoclax/obinutuzumab (12 months) or chemoimmunotherapy (usually 6 months).	ibrutinib	251-260	tumor protein p53	Homo sapiens	55-59
31375978-0	2020	Ibrutinib as a potential therapeutic option for HER2 overexpressing breast cancer - the role of STAT3 and p21.	ibrutinib	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	48-52
32631091-4	2020	Clinical trial data that led to the approval of ibrutinib (the first-in-class BTKi) will be reviewed.	ibrutinib	48-57	inhibitor of Bruton tyrosine kinase	Homo sapiens	78-82
32673127-1	2020	INTRODUCTION: Development of the BTK inhibitor ibrutinib has changed the landscape of CLL treatment producing durable responses with minimal to no myelosuppression.	ibrutinib	47-56	Bruton tyrosine kinase	Homo sapiens	33-36
32673127-3	2020	AREAS COVERED: Data from recent studies indicate that most patients relapsing on ibrutinib have mutations in BTK or PLCG2.	ibrutinib	81-90	Bruton tyrosine kinase	Homo sapiens	109-112
32673127-3	2020	AREAS COVERED: Data from recent studies indicate that most patients relapsing on ibrutinib have mutations in BTK or PLCG2.	ibrutinib	81-90	phospholipase C gamma 2	Homo sapiens	116-121
32673127-4	2020	The result of the C418S mutation in BTK is loss of covalent binding of ibrutinib to BTK resulting in reversible, transient inhibition in BTK mutant patients.	ibrutinib	71-80	Bruton tyrosine kinase	Homo sapiens	36-39
32673127-4	2020	The result of the C418S mutation in BTK is loss of covalent binding of ibrutinib to BTK resulting in reversible, transient inhibition in BTK mutant patients.	ibrutinib	71-80	Bruton tyrosine kinase	Homo sapiens	84-87
32673127-4	2020	The result of the C418S mutation in BTK is loss of covalent binding of ibrutinib to BTK resulting in reversible, transient inhibition in BTK mutant patients.	ibrutinib	71-80	Bruton tyrosine kinase	Homo sapiens	84-87
32673127-5	2020	There is downstream gain of function of BCR signaling with PLCG2 mutations allowing continued cell proliferation despite inhibition of BTK by ibrutinib.	ibrutinib	142-151	phospholipase C gamma 2	Homo sapiens	59-64
32673127-5	2020	There is downstream gain of function of BCR signaling with PLCG2 mutations allowing continued cell proliferation despite inhibition of BTK by ibrutinib.	ibrutinib	142-151	Bruton tyrosine kinase	Homo sapiens	135-138
32673127-8	2020	EXPERT OPINION: The current approach is to offer a clinical trial or the BCL2 inhibitor venetoclax to patients with ibrutinib resistant CLL.	ibrutinib	116-125	BCL2 apoptosis regulator	Homo sapiens	73-77
32673127-9	2020	We await more data from ongoing clinical trials combining different targeted therapies or using reversible BTK inhibitors will provide more options for overcoming ibrutinib resistance.	ibrutinib	163-172	Bruton tyrosine kinase	Homo sapiens	107-110
32702393-5	2020	Inhibition of MiR-155 decreased expression of NFkappaB target genes and sensitized DLBCL cells to ibrutinib, confirming the role of MiR-155 in the modulation of BCR signaling.	ibrutinib	98-107	microRNA 155	Homo sapiens	14-21
32053229-2	2020	Ibrutinib is a first-in-class, once-daily inhibitor of Bruton"s tyrosine kinase, an enzyme implicated in growth and survival of MM cells.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	55-79
31375978-3	2020	Ibrutinib is a recently approved Tyrosine Kinase Inhibitor (TKI) that has been shown be an effective therapeutic option for HER2 overexpressing breast cancer.	ibrutinib	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	124-128
31375978-4	2020	The molecular mechanisms, pathways, or genes that are modulated by ibrutinib and the mechanism of action of ibrutinib in HER2 overexpressing breast cancer remain obscure.	ibrutinib	108-117	erb-b2 receptor tyrosine kinase 2	Homo sapiens	121-125
31375978-5	2020	In this study, we have performed a kinome array analysis of ibrutinib treatment in two HER2 overexpressing breast cancer cell lines.	ibrutinib	60-69	erb-b2 receptor tyrosine kinase 2	Homo sapiens	87-91
31375978-6	2020	Our analysis shows that ibrutinib induces changes in nuclear morphology and causes apoptosis via caspase-dependent extrinsic apoptosis pathway with the activation of caspases-8, caspase-3, and cleavage of PARP1.	ibrutinib	24-33	caspase 3	Homo sapiens	178-187
31375978-6	2020	Our analysis shows that ibrutinib induces changes in nuclear morphology and causes apoptosis via caspase-dependent extrinsic apoptosis pathway with the activation of caspases-8, caspase-3, and cleavage of PARP1.	ibrutinib	24-33	poly(ADP-ribose) polymerase 1	Homo sapiens	205-210
31375978-9	2020	These results suggest that inhibitors of STAT3 phosphorylation may be potential options for combination therapy to help increase the efficacy of ibrutinib against HER2-overexpressing tumors.	ibrutinib	145-154	signal transducer and activator of transcription 3	Homo sapiens	41-46
31375978-9	2020	These results suggest that inhibitors of STAT3 phosphorylation may be potential options for combination therapy to help increase the efficacy of ibrutinib against HER2-overexpressing tumors.	ibrutinib	145-154	erb-b2 receptor tyrosine kinase 2	Homo sapiens	163-167
32790160-2	2020	ZYBT1 is a potent, irreversible, specific BTK inhibitor that inhibits the ibrutinib-resistant C481S BTK with nanomolar potency.	ibrutinib	74-83	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	42-45
32691208-11	2020	Interestingly, treatment with selinexor and ibrutinib favored an anti-tumoral immune response by shifting polarization toward inflammatory M1-like and diminishing PD-1 and SIRPalpha expression in the remaining tumor-promoting M2-like macrophages.	ibrutinib	44-53	programmed cell death 1	Mus musculus	163-167
32691208-11	2020	Interestingly, treatment with selinexor and ibrutinib favored an anti-tumoral immune response by shifting polarization toward inflammatory M1-like and diminishing PD-1 and SIRPalpha expression in the remaining tumor-promoting M2-like macrophages.	ibrutinib	44-53	signal-regulatory protein alpha	Mus musculus	172-181
32790160-2	2020	ZYBT1 is a potent, irreversible, specific BTK inhibitor that inhibits the ibrutinib-resistant C481S BTK with nanomolar potency.	ibrutinib	74-83	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	100-103
32732360-0	2021	Impaired nodal shrinkage and apoptosis define the independent adverse outcome of NOTCH1 mutated patients under ibrutinib therapy in chronic lymphocytic leukaemia.	ibrutinib	111-120	notch receptor 1	Homo sapiens	81-87
32732360-5	2021	NOTCH1 mutations (M) were correlated with a reduced redistribution lymphocytosis, calculated at 3 months on ibrutinib (p=0.022).	ibrutinib	108-117	notch receptor 1	Homo sapiens	0-6
32732360-6	2021	Moreover, NOTCH1 mutated patients showed inferior nodal response at 6 months on ibrutinib compared to NOTCH1 wild type patients (p<0.0001).	ibrutinib	80-89	notch receptor 1	Homo sapiens	10-16
32732360-10	2021	In conclusion, NOTCH1 M are strongly associated with lower bax/bcl-2 ratio, consistent with a defective apoptosis, lower redistribution lymphocytosis and lower nodal shrinkage under ibrutinib treatment, this last responsible for partial responses, subsequent relapses, shorter PFS and OS.	ibrutinib	182-191	notch receptor 1	Homo sapiens	15-21
32732360-10	2021	In conclusion, NOTCH1 M are strongly associated with lower bax/bcl-2 ratio, consistent with a defective apoptosis, lower redistribution lymphocytosis and lower nodal shrinkage under ibrutinib treatment, this last responsible for partial responses, subsequent relapses, shorter PFS and OS.	ibrutinib	182-191	BCL2 associated X, apoptosis regulator	Homo sapiens	59-62
32732360-10	2021	In conclusion, NOTCH1 M are strongly associated with lower bax/bcl-2 ratio, consistent with a defective apoptosis, lower redistribution lymphocytosis and lower nodal shrinkage under ibrutinib treatment, this last responsible for partial responses, subsequent relapses, shorter PFS and OS.	ibrutinib	182-191	BCL2 apoptosis regulator	Homo sapiens	63-68
32726539-0	2020	Ibrutinib for Chronic Lymphocytic Leukemia with TP53 Alterations.	ibrutinib	0-9	tumor protein p53	Homo sapiens	48-52
32732361-6	2021	Moreover, we demonstrate that CLL cells with inactive-HS1, impaired cytoskeletal activity and a more aggressive phenotype are more likely retained within the scaffold despite the presence of Ibrutinib, whose mobilizing effect is mainly exerted on those with active-HS1, ensuing dynamic cytoskeletal activity.	ibrutinib	191-200	hematopoietic cell-specific Lyn substrate 1	Homo sapiens	265-268
32732361-8	2021	Notably, CLL cells mobilized in the peripheral blood of patients during Ibrutinib therapy exhibited activated HS1, underscoring that our model reliably mirrors the in vivo situation.	ibrutinib	72-81	hematopoietic cell-specific Lyn substrate 1	Homo sapiens	110-113
32369353-9	2020	The PROTACs showed enhanced inhibition of B cell activation compared to Ibrutinib, and exhibit potent degradation of BTK in patients-derived primary chronic lymphocytic leukemia cells.	ibrutinib	72-81	Bruton tyrosine kinase	Homo sapiens	117-120
32654665-11	2020	Allele-specific polymerase chain reaction is a sensitive assay for detecting MYD88 L265P mutations in pleural fluid to support the diagnosis of malignant pleural effusion in the setting of Waldenstrom"s macroglobulinemia and helps guide the treatment decision to use ibrutinib.	ibrutinib	267-276	MYD88 innate immune signal transduction adaptor	Homo sapiens	77-82
32664705-2	2020	Particularly, understanding the role of Bruton tyrosine kinase and phosphatidyl inositol 3 kinase delta in driving prosurvival signal transduction in chronic lymphocytic leukemia (CLL) cells and their targeting with pharmacological inhibitors (ibrutinib and idelalisib, respectively) has improved patient outcomes significantly.	ibrutinib	244-253	Bruton tyrosine kinase	Homo sapiens	40-62
32664705-9	2020	The inhibition of DNPEP with a pharmacological inhibitor enhanced the cytotoxic potential of idelalisib and ibrutinib, indicating a biological functionality of DNPEP in CLL.	ibrutinib	108-117	aspartyl aminopeptidase	Homo sapiens	18-23
32664705-9	2020	The inhibition of DNPEP with a pharmacological inhibitor enhanced the cytotoxic potential of idelalisib and ibrutinib, indicating a biological functionality of DNPEP in CLL.	ibrutinib	108-117	aspartyl aminopeptidase	Homo sapiens	160-165
32418995-5	2020	RESULTS: High UGT2B17 in B-cell models led to reduced sensitivity to fludarabine, ibrutinib and idelalisib.	ibrutinib	82-91	UDP glucuronosyltransferase family 2 member B17	Homo sapiens	14-21
32146518-9	2020	The inhibition of BTK by ibrutinib mimicked the effect of ADO, and ibrutinib reduced the production of ADO by downregulation of CD39 in vitro.	ibrutinib	25-34	Bruton tyrosine kinase	Homo sapiens	18-21
32197990-1	2020	INTRODUCTION: The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has transformed the treatment of chronic lymphocytic leukemia (CLL), leading to unprecedented improvements in progression-free and overall survival for all patients, including those with poor prognostic features.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	18-42
32146518-9	2020	The inhibition of BTK by ibrutinib mimicked the effect of ADO, and ibrutinib reduced the production of ADO by downregulation of CD39 in vitro.	ibrutinib	67-76	ectonucleoside triphosphate diphosphohydrolase 1	Homo sapiens	128-132
32420699-7	2020	In addition, we found favorable combinatory growth inhibitory effects of BI-D1870 with inhibitors of BTK (ibrutinib), AKT (ipatasertib), and BCL2 (venetoclax) in cell characteristic-dependent manners.	ibrutinib	106-115	Bruton tyrosine kinase	Homo sapiens	101-104
32197990-1	2020	INTRODUCTION: The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has transformed the treatment of chronic lymphocytic leukemia (CLL), leading to unprecedented improvements in progression-free and overall survival for all patients, including those with poor prognostic features.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	44-47
32643971-8	2020	Subsequently, the histone deacetylase (HDAC) inhibitor chidamide and Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib were concurrently administered, and the patient achieved complete remission.	ibrutinib	110-119	Bruton tyrosine kinase	Homo sapiens	69-93
32643971-8	2020	Subsequently, the histone deacetylase (HDAC) inhibitor chidamide and Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib were concurrently administered, and the patient achieved complete remission.	ibrutinib	110-119	Bruton tyrosine kinase	Homo sapiens	95-98
32532074-9	2020	Ibrutinib exerts multiple antineoplastic effects, such as on-target BTK inhibition, off-target kinase inhibition, and immunomodulation by interference with myeloid-derived suppressor cells (MDSCs), programmed death-ligand 1 (PD-L1), and T cell response.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	68-71
32924028-2	2020	The Bruton tyrosine kinase (BTK) is an important mediator of B-cell receptor signaling and the irreversible BTK inhibitor ibrutinib can trigger dramatic clinical responses in treated patients.	ibrutinib	122-131	Bruton tyrosine kinase	Homo sapiens	4-26
32924028-2	2020	The Bruton tyrosine kinase (BTK) is an important mediator of B-cell receptor signaling and the irreversible BTK inhibitor ibrutinib can trigger dramatic clinical responses in treated patients.	ibrutinib	122-131	Bruton tyrosine kinase	Homo sapiens	28-31
32924028-2	2020	The Bruton tyrosine kinase (BTK) is an important mediator of B-cell receptor signaling and the irreversible BTK inhibitor ibrutinib can trigger dramatic clinical responses in treated patients.	ibrutinib	122-131	Bruton tyrosine kinase	Homo sapiens	108-111
32924028-5	2020	In this review, we discuss recent progress in the development of BTK-targeted proteolysis targeting chimeras (PROTACs) describing how such agents may provide advantages over ibrutinib and highlighting features of PROTACs that are important for the development of effective BTK degrading agents.	ibrutinib	174-183	Bruton tyrosine kinase	Homo sapiens	65-68
32234429-8	2020	Therapeutic treatment with Ibrutinib caused attenuation of IMQ-induced oxidative stress in CD11c + DCs and neutrophils.	ibrutinib	27-36	integrin alpha X	Mus musculus	91-96
32234429-9	2020	Further there were dysregulations in antioxidants enzymes (SOD/GPx/GR) in the skin of IMQ-treated mice, which were corrected by Ibrutinib.	ibrutinib	128-137	glutathione reductase	Mus musculus	67-69
32532074-9	2020	Ibrutinib exerts multiple antineoplastic effects, such as on-target BTK inhibition, off-target kinase inhibition, and immunomodulation by interference with myeloid-derived suppressor cells (MDSCs), programmed death-ligand 1 (PD-L1), and T cell response.	ibrutinib	0-9	CD274 molecule	Homo sapiens	198-223
32532074-9	2020	Ibrutinib exerts multiple antineoplastic effects, such as on-target BTK inhibition, off-target kinase inhibition, and immunomodulation by interference with myeloid-derived suppressor cells (MDSCs), programmed death-ligand 1 (PD-L1), and T cell response.	ibrutinib	0-9	CD274 molecule	Homo sapiens	225-230
32459810-0	2020	Structure-based drug repositioning explains ibrutinib as VEGFR2 inhibitor.	ibrutinib	44-53	kinase insert domain receptor	Homo sapiens	57-63
32232486-0	2020	Novel BCL2 mutations in venetoclax-resistant, ibrutinib-resistant CLL patients with BTK/PLCG2 mutations.	ibrutinib	46-55	BCL2 apoptosis regulator	Homo sapiens	6-10
32232486-0	2020	Novel BCL2 mutations in venetoclax-resistant, ibrutinib-resistant CLL patients with BTK/PLCG2 mutations.	ibrutinib	46-55	Bruton tyrosine kinase	Homo sapiens	84-87
32232486-0	2020	Novel BCL2 mutations in venetoclax-resistant, ibrutinib-resistant CLL patients with BTK/PLCG2 mutations.	ibrutinib	46-55	phospholipase C gamma 2	Homo sapiens	88-93
32503582-1	2020	BACKGROUND: Ibrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL) in 2014.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	27-49
32582577-4	2020	Ibrutinib, a BTK inhibitor, is approved for the treatment of several B cell malignancies, including some types of lymphoma and leukemia.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-16
32103491-1	2020	Ibrutinib is highly active in Waldenstrom macroglobulinaemia (WM) patients, but disease progression can occur due to acquired mutations in BTK, the target of ibrutinib, or PLCG2, the protein downstream of BTK.	ibrutinib	0-9	phospholipase C gamma 2	Homo sapiens	172-177
32103491-1	2020	Ibrutinib is highly active in Waldenstrom macroglobulinaemia (WM) patients, but disease progression can occur due to acquired mutations in BTK, the target of ibrutinib, or PLCG2, the protein downstream of BTK.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	205-208
32103491-1	2020	Ibrutinib is highly active in Waldenstrom macroglobulinaemia (WM) patients, but disease progression can occur due to acquired mutations in BTK, the target of ibrutinib, or PLCG2, the protein downstream of BTK.	ibrutinib	158-167	Bruton tyrosine kinase	Homo sapiens	139-142
32103491-5	2020	Moreover, we have identified recurring mutations in ubiquitin ligases, innate immune signalling, and TLR/MYD88 pathway regulators in ibrutinib-resistant WM patients.	ibrutinib	133-142	MYD88 innate immune signal transduction adaptor	Homo sapiens	105-110
32415406-1	2020	PURPOSE OF REVIEW: Ibrutinib is a first-in-class, highly potent Bruton tyrosine kinase inhibitor which has become standard of care for patients with chronic lymphocytic leukaemia and other lymphoproliferative disorders.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	64-86
32482755-7	2020	This is underscored by the observation that CD20 is decreased in response to the "BCR inhibitor" ibrutinib which largely prevents its successful combination with rituximab.	ibrutinib	97-106	membrane spanning 4-domains A1	Homo sapiens	44-48
32581054-5	2020	RESULTS: Here, we report that a bispecific CD3xCD19 DART mediates efficient killing by HD T cells of CD19+ cell-lines and primary CLL cells, regardless of immunoglobulin heavy chain variable region (IGHV) mutational status TP53 status or chemotherapy, ibrutinib or venetoclax sensitivity.	ibrutinib	252-261	CD19 molecule	Homo sapiens	43-51
32581054-5	2020	RESULTS: Here, we report that a bispecific CD3xCD19 DART mediates efficient killing by HD T cells of CD19+ cell-lines and primary CLL cells, regardless of immunoglobulin heavy chain variable region (IGHV) mutational status TP53 status or chemotherapy, ibrutinib or venetoclax sensitivity.	ibrutinib	252-261	CD19 molecule	Homo sapiens	47-51
31862959-1	2020	Despite major improvements in treatment outcome with novel targeted therapies, such as the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, chronic lymphocytic leukemia (CLL) remains incurable in the majority of patients.	ibrutinib	130-139	Bruton tyrosine kinase	Homo sapiens	91-113
31862959-1	2020	Despite major improvements in treatment outcome with novel targeted therapies, such as the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, chronic lymphocytic leukemia (CLL) remains incurable in the majority of patients.	ibrutinib	130-139	Bruton tyrosine kinase	Homo sapiens	115-118
31862959-2	2020	Activation of PI3K, NF-kappaB, and/or MYC has been linked to residual disease and/or resistance in ibrutinib-treated patients.	ibrutinib	99-108	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	38-41
31974435-6	2020	Ex vivo studies in the presence of stromal stimulation on 38 CLL primary samples confirmed a synergistic action of the combination of olaparib and ibrutinib in del(11q)/ATM-mutated CLL patients.	ibrutinib	147-156	ATM serine/threonine kinase	Homo sapiens	169-172
31974435-7	2020	In addition, we showed that ibrutinib produced a homologous recombination repair impairment through RAD51 dysregulation, finding a synergistic link of both drugs in the DNA damage repair pathway.	ibrutinib	28-37	RAD51 recombinase	Homo sapiens	100-105
32306542-5	2020	DAPK inhibition mimics ibrutinib-induced repression of both IEG mRNA and histone H3 phosphorylation and has anti-proliferative effect comparable to ibrutinib in CLL in vitro.	ibrutinib	23-32	death associated protein kinase 1	Homo sapiens	0-4
32306542-6	2020	DAPK inhibitor (DAPKi) does not repress transcription itself but impacts on mRNA processing and has a broader anti-tumour effect than ibrutinib, by repressing both anti-IgM- and CD40L-dependent activation.	ibrutinib	134-143	death associated protein kinase 1	Homo sapiens	0-4
32349864-0	2020	B-cell prolymphocytic leukaemia with a t(4;14) FGFR3/IGH translocation: response to ibrutinib.	ibrutinib	84-93	fibroblast growth factor receptor 3	Homo sapiens	47-52
32349864-0	2020	B-cell prolymphocytic leukaemia with a t(4;14) FGFR3/IGH translocation: response to ibrutinib.	ibrutinib	84-93	immunoglobulin heavy locus	Homo sapiens	53-56
32581549-2	2020	Ibrutinib is a highly active and selectively irreversible inhibitor of BTK, which has been approved to be effective in both frontline and recurrent therapy of CLL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	71-74
32459810-7	2020	The main result of this paper is that structure-based drug repositioning for the identified kinase targets identified the cancer drug ibrutinib as micromolar VEGFR2 inhibitor with a very high therapeutic index in B-cell inactivation.	ibrutinib	134-143	kinase insert domain receptor	Homo sapiens	158-164
32459810-8	2020	These findings prove that ibrutinib is not only acting on the Bruton"s tyrosine kinase BTK, against which it was designed.	ibrutinib	26-35	Bruton tyrosine kinase	Homo sapiens	62-86
32459810-8	2020	These findings prove that ibrutinib is not only acting on the Bruton"s tyrosine kinase BTK, against which it was designed.	ibrutinib	26-35	Bruton tyrosine kinase	Homo sapiens	87-90
32459810-10	2020	Therefore ibrutinib carries potential to treat other VEGFR2 associated disease.	ibrutinib	10-19	kinase insert domain receptor	Homo sapiens	53-59
32459810-11	2020	Structure-based drug repositioning explains ibrutinib"s anti VEGFR2 action through the conservation of a specific pattern of interactions of the drug with BTK and VEGFR2.	ibrutinib	44-53	kinase insert domain receptor	Homo sapiens	61-67
32459810-11	2020	Structure-based drug repositioning explains ibrutinib"s anti VEGFR2 action through the conservation of a specific pattern of interactions of the drug with BTK and VEGFR2.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	155-158
32459810-11	2020	Structure-based drug repositioning explains ibrutinib"s anti VEGFR2 action through the conservation of a specific pattern of interactions of the drug with BTK and VEGFR2.	ibrutinib	44-53	kinase insert domain receptor	Homo sapiens	163-169
32302379-0	2020	The BTK inhibitor ibrutinib may protect against pulmonary injury in COVID-19-infected patients.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
32455989-2	2020	Although the BTK-targeting agent ibrutinib has shown promising clinical responses, the presence of primary or acquired resistance is common and often leads to dismal clinical outcomes.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	13-16
34055615-0	2021	Proteolysis Targeting Chimeras for BTK Efficiently Inhibit B-Cell Receptor Signaling and Can Overcome Ibrutinib Resistance in CLL Cells.	ibrutinib	102-111	Bruton tyrosine kinase	Homo sapiens	35-38
32494164-7	2020	Overexpressing BTK could partially but significantly block the inhibitory effect of Ibrutinib on cell proliferation, migration and invasion, and protein synthesis of MMP-2 and MMP-9 of the cancer cells.	ibrutinib	84-93	Bruton tyrosine kinase	Homo sapiens	15-18
32647793-8	2020	CXCR4 mutations impacted response and survival outcomes to ibrutinib monotherapy.	ibrutinib	59-68	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
32253666-6	2020	However, atrial fibrillation and bleeding are associated with the BTK inhibitor, ibrutinib, while tumor lysis syndrome is an adverse event (AE) of the BCL-2 inhibitor, venetoclax.	ibrutinib	81-90	Bruton tyrosine kinase	Homo sapiens	66-69
32494164-0	2020	Bruton"s Tyrosine Kinase (BTK) Inhibitor (Ibrutinib)-Suppressed Migration and Invasion of Prostate Cancer.	ibrutinib	42-51	Bruton tyrosine kinase	Homo sapiens	0-24
32494164-0	2020	Bruton"s Tyrosine Kinase (BTK) Inhibitor (Ibrutinib)-Suppressed Migration and Invasion of Prostate Cancer.	ibrutinib	42-51	Bruton tyrosine kinase	Homo sapiens	26-29
32494164-6	2020	BTK inhibitor (Ibrutinib) significantly inhibited cell proliferation, migration and invasion of prostate cancer cells as well as protein synthesis of MMP-2 and MMP-9 by the tumor cells.	ibrutinib	15-24	Bruton tyrosine kinase	Homo sapiens	0-3
32494164-6	2020	BTK inhibitor (Ibrutinib) significantly inhibited cell proliferation, migration and invasion of prostate cancer cells as well as protein synthesis of MMP-2 and MMP-9 by the tumor cells.	ibrutinib	15-24	matrix metallopeptidase 2	Homo sapiens	150-155
32494164-6	2020	BTK inhibitor (Ibrutinib) significantly inhibited cell proliferation, migration and invasion of prostate cancer cells as well as protein synthesis of MMP-2 and MMP-9 by the tumor cells.	ibrutinib	15-24	matrix metallopeptidase 9	Homo sapiens	160-165
32187452-6	2020	On multivariable analyses, temporary ibrutinib interruption (hazard ratio [HR]: 2.37, P = .006) and TP53 disruption at ibrutinib initiation (HR: 1.81, P = .048) were associated with shorter EFS, whereas only TP53 disruption (HR: 2.38, P = .015) was associated with shorter OS.	ibrutinib	119-128	tumor protein p53	Homo sapiens	100-104
32186759-17	2020	In brief, EGFR overexpression can reverse the resistance of DLBCL to ibrutinib via PDGFD interference, and PDGFD induces the resistance of DLBCL to ibrutinib via EGFR.	ibrutinib	148-157	platelet derived growth factor D	Homo sapiens	107-112
32467812-1	2020	Ibrutinib is a Bruton tyrosine kinase (BTK) inhibitor that has shown significant efficacy in patients with lymphoid carcinomas, mostly chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	15-37
32467812-1	2020	Ibrutinib is a Bruton tyrosine kinase (BTK) inhibitor that has shown significant efficacy in patients with lymphoid carcinomas, mostly chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	39-42
32184360-0	2020	Non-catalytic Bruton"s tyrosine kinase activates PLCgamma2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells.	ibrutinib	78-87	Bruton tyrosine kinase	Homo sapiens	14-38
32184360-0	2020	Non-catalytic Bruton"s tyrosine kinase activates PLCgamma2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells.	ibrutinib	78-87	phospholipase C gamma 2	Homo sapiens	49-58
32184360-1	2020	Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton"s tyrosine kinase (BTK) such as ibrutinib is limited by primary or secondary resistance to this drug.	ibrutinib	120-129	Bruton tyrosine kinase	Homo sapiens	81-105
32184360-1	2020	Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton"s tyrosine kinase (BTK) such as ibrutinib is limited by primary or secondary resistance to this drug.	ibrutinib	120-129	Bruton tyrosine kinase	Homo sapiens	107-110
32184360-2	2020	Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK"s catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-gamma2 (PLCgamma2).	ibrutinib	57-66	Bruton tyrosine kinase	Homo sapiens	83-86
32076701-0	2020	Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure.	ibrutinib	94-103	CXADR pseudogene 1	Homo sapiens	42-45
32076701-1	2020	We previously reported durable responses in relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) patients treated with CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T-cell immunotherapy after ibrutinib failure.	ibrutinib	219-228	CXADR pseudogene 1	Homo sapiens	187-190
32076701-2	2020	Because preclinical studies showed that ibrutinib could improve CAR T cell-antitumor efficacy and reduce cytokine release syndrome (CRS), we conducted a pilot study to evaluate the safety and feasibility of administering ibrutinib concurrently with CD19 CAR T-cell immunotherapy.	ibrutinib	40-49	CXADR pseudogene 1	Homo sapiens	64-67
32076701-11	2020	CD19 CAR T cells with concurrent ibrutinib for R/R CLL were well tolerated, with low CRS severity, and led to high rates of MRD-negative response by IGH sequencing.	ibrutinib	33-42	CXADR pseudogene 1	Homo sapiens	5-8
32076701-11	2020	CD19 CAR T cells with concurrent ibrutinib for R/R CLL were well tolerated, with low CRS severity, and led to high rates of MRD-negative response by IGH sequencing.	ibrutinib	33-42	immunoglobulin heavy locus	Homo sapiens	149-152
32064588-7	2020	BMX plays a crucial role in the Bruton"s Tyrosine Kinase (BTK) pathway which is bound by the BTK inhibitor, ibrutinib, suggesting adult B-ALL would also be a worthy target patient group for future clinical trials.	ibrutinib	108-117	BMX non-receptor tyrosine kinase	Homo sapiens	0-3
32064588-7	2020	BMX plays a crucial role in the Bruton"s Tyrosine Kinase (BTK) pathway which is bound by the BTK inhibitor, ibrutinib, suggesting adult B-ALL would also be a worthy target patient group for future clinical trials.	ibrutinib	108-117	Bruton tyrosine kinase	Homo sapiens	32-56
32064588-7	2020	BMX plays a crucial role in the Bruton"s Tyrosine Kinase (BTK) pathway which is bound by the BTK inhibitor, ibrutinib, suggesting adult B-ALL would also be a worthy target patient group for future clinical trials.	ibrutinib	108-117	Bruton tyrosine kinase	Homo sapiens	58-61
32064588-7	2020	BMX plays a crucial role in the Bruton"s Tyrosine Kinase (BTK) pathway which is bound by the BTK inhibitor, ibrutinib, suggesting adult B-ALL would also be a worthy target patient group for future clinical trials.	ibrutinib	108-117	Bruton tyrosine kinase	Homo sapiens	93-96
31883396-1	2020	OBJECTIVE: We evaluated ibrutinib, a once-daily inhibitor of Bruton"s tyrosine kinase, combined with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma who had received 1-3 prior therapies.	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	61-85
31899702-0	2020	Antitumor Potency of an Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, Lisocabtagene Maraleucel in Combination With Ibrutinib or Acalabrutinib.	ibrutinib	121-130	CD19 molecule	Homo sapiens	29-33
31899702-7	2020	Ibrutinib or acalabrutinib improved CD19 tumor clearance and prolonged survival of tumor-bearing mice when used in combination with CAR T cells.	ibrutinib	0-9	CD19 antigen	Mus musculus	36-40
31899702-8	2020	A combination of the defined cell product therapy candidate, liso-cel, with ibrutinib or acalabrutinib is an attractive approach that may potentiate the promising clinical responses already achieved in CD19 B-cell malignancies with each of these single agents.	ibrutinib	76-85	CD19 molecule	Homo sapiens	202-206
32272741-3	2020	Here is described the development of a model to screen a library of kinase inhibitors for collateral sensitivity drugs active on the Bruton Tyrosine Kinase (BTK) protein with the ibrutinib resistance mutation C481S.	ibrutinib	179-188	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	133-155
32070760-0	2020	Enhanced Solid-State Stability of Amorphous Ibrutinib Formulations Prepared by Hot-Melt Extrusion.	ibrutinib	44-53	alcohol dehydrogenase iron containing 1	Homo sapiens	79-82
32083995-5	2020	Responses to many agents commonly used to treat WM, including the BTK inhibitor ibrutinib, are affected by MYD88 and/or CXCR4 mutation status.	ibrutinib	80-89	Bruton tyrosine kinase	Homo sapiens	66-69
32083995-5	2020	Responses to many agents commonly used to treat WM, including the BTK inhibitor ibrutinib, are affected by MYD88 and/or CXCR4 mutation status.	ibrutinib	80-89	MYD88 innate immune signal transduction adaptor	Homo sapiens	107-112
32083995-5	2020	Responses to many agents commonly used to treat WM, including the BTK inhibitor ibrutinib, are affected by MYD88 and/or CXCR4 mutation status.	ibrutinib	80-89	C-X-C motif chemokine receptor 4	Homo sapiens	120-125
32272741-3	2020	Here is described the development of a model to screen a library of kinase inhibitors for collateral sensitivity drugs active on the Bruton Tyrosine Kinase (BTK) protein with the ibrutinib resistance mutation C481S.	ibrutinib	179-188	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	157-160
31953125-1	2020	BACKGROUND: Bruton"s tyrosine kinase (BTK) is a key component of the B-cell receptor (BCR) pathway and a clinically validated target for small molecule inhibitors such as ibrutinib in the treatment of B-cell malignancies.	ibrutinib	171-180	Bruton tyrosine kinase	Homo sapiens	12-36
31931656-8	2020	The mass showed no reduction after three cycles of R-MINE, following which the BTK inhibitor ibrutinib was administered to this patient.	ibrutinib	93-102	Bruton tyrosine kinase	Homo sapiens	79-82
31837347-4	2020	Further data using the TFK inhibitor Ibrutinib indicated that BTK Y223 is phosphorylated by a non-BTK TFK upon SCF stimulation.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	62-65
31837347-4	2020	Further data using the TFK inhibitor Ibrutinib indicated that BTK Y223 is phosphorylated by a non-BTK TFK upon SCF stimulation.	ibrutinib	37-46	KIT ligand	Homo sapiens	111-114
31837347-5	2020	In line, SCF-induced PLCgamma1 phosphorylation was stronger attenuated by Ibrutinib than by BTK deficiency.	ibrutinib	74-83	KIT ligand	Homo sapiens	9-12
31837347-5	2020	In line, SCF-induced PLCgamma1 phosphorylation was stronger attenuated by Ibrutinib than by BTK deficiency.	ibrutinib	74-83	phospholipase C gamma 1	Homo sapiens	21-30
32017058-0	2020	The Bruton"s tyrosine kinase inhibitor ibrutinib abrogates bispecific antibody-mediated T-cell cytotoxicity.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	4-28
31953125-1	2020	BACKGROUND: Bruton"s tyrosine kinase (BTK) is a key component of the B-cell receptor (BCR) pathway and a clinically validated target for small molecule inhibitors such as ibrutinib in the treatment of B-cell malignancies.	ibrutinib	171-180	Bruton tyrosine kinase	Homo sapiens	38-41
31831562-7	2020	AQX-435 also co-operated with the BTK inhibitor ibrutinib to enhance inhibition of anti-IgM-induced AKT phosphorylation.	ibrutinib	48-57	Bruton tyrosine kinase	Homo sapiens	34-37
31831562-10	2020	CONCLUSIONS: Our results using AQX-435 demonstrate that SHIP1 activation may be an effective novel therapeutic strategy for treatment of B-cell neoplasms, alone or in combination with ibrutinib.	ibrutinib	184-193	inositol polyphosphate-5-phosphatase D	Homo sapiens	56-61
32034308-5	2020	This stabilization was hampered by the BCR-pathway inhibitor Ibrutinib, supporting beta-catenin as an effector of the BCR signaling.	ibrutinib	61-70	catenin beta 1	Homo sapiens	83-95
31922303-9	2020	This is the first report about obinutuzumab and venetoclax induced CR in rituximab-intolerant patient with an ibrutinib-resistant MCL.	ibrutinib	110-119	C-type lectin domain family 4 member D	Homo sapiens	130-133
31922303-10	2020	This case suggests that obinutuzumab and venetoclax based combination therapy might be salvage therapy in patients with ibrutinib-resistant MCL.	ibrutinib	120-129	C-type lectin domain family 4 member D	Homo sapiens	140-143
31732977-1	2020	A major revolution in the treatment of chronic lymphocytic leukemia (CLL) began with the approval of ibrutinib, a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK), for the treatment of relapsed/refractory (R/R) and/or TP53 mutated patients with CLL.	ibrutinib	101-110	Bruton tyrosine kinase	Homo sapiens	147-169
31732977-1	2020	A major revolution in the treatment of chronic lymphocytic leukemia (CLL) began with the approval of ibrutinib, a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK), for the treatment of relapsed/refractory (R/R) and/or TP53 mutated patients with CLL.	ibrutinib	101-110	Bruton tyrosine kinase	Homo sapiens	171-174
31732977-1	2020	A major revolution in the treatment of chronic lymphocytic leukemia (CLL) began with the approval of ibrutinib, a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK), for the treatment of relapsed/refractory (R/R) and/or TP53 mutated patients with CLL.	ibrutinib	101-110	tumor protein p53	Homo sapiens	231-235
31732977-5	2020	A possible strategy to overcome some of these obstacles is to combine ibrutinib with other targeted agents especially in high-risk disease, such as previously treated refractory patients or those with TP53 aberrations or complex karyotypes, in whom rapid eradication of disease is most desirable.	ibrutinib	70-79	tumor protein p53	Homo sapiens	201-205
31895698-3	2020	We found that bone marrow-derived macrophages (BMDMs) from BTK-deficient mice or monocytes from X-linked agammaglobulinemia patients exhibit increased NLRP3 inflammasome activity; this was also the case with BMDMs exposed to low doses of BTK inhibitor such as ibrutinib and monocytes from chronic lymphocytic leukemia patients being treated with ibrutinib.	ibrutinib	260-269	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	59-62
31895698-3	2020	We found that bone marrow-derived macrophages (BMDMs) from BTK-deficient mice or monocytes from X-linked agammaglobulinemia patients exhibit increased NLRP3 inflammasome activity; this was also the case with BMDMs exposed to low doses of BTK inhibitor such as ibrutinib and monocytes from chronic lymphocytic leukemia patients being treated with ibrutinib.	ibrutinib	346-355	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	59-62
32239385-0	2020	Genomic Alterations and MYD88MUT Variant Mapping in Patients with Diffuse Large B-Cell Lymphoma and Response to Ibrutinib.	ibrutinib	112-121	MYD88 innate immune signal transduction adaptor	Homo sapiens	24-29
32239385-3	2020	It has been previously reported that MYD88MUT affects the response to ibrutinib in patients with r/r DLBCL.	ibrutinib	70-79	MYD88 innate immune signal transduction adaptor	Homo sapiens	37-42
32319422-4	2020	To date, the BTK inhibitor Ibrutinib, PI3K inhibitors Idelalisib and Duvelisib have been approved for CLL treatment, and some novel inhibitors are still in clinical trials.	ibrutinib	27-36	Bruton tyrosine kinase	Homo sapiens	13-16
32228672-5	2020	Here, we investigated the therapeutic potential of ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor used in B cell malignancies, to alter B cell pathology in SSc in an in vitro model of autoimmunity.	ibrutinib	51-60	Bruton tyrosine kinase	Homo sapiens	90-93
32228672-8	2020	RESULTS: Ibrutinib was able to reduce the production of the profibrotic hallmark cytokines IL-6 and TNF-alpha mainly from the effector B cell population in patients with SSc.	ibrutinib	9-18	interleukin 6	Homo sapiens	91-95
32228672-8	2020	RESULTS: Ibrutinib was able to reduce the production of the profibrotic hallmark cytokines IL-6 and TNF-alpha mainly from the effector B cell population in patients with SSc.	ibrutinib	9-18	tumor necrosis factor	Homo sapiens	100-109
32228672-9	2020	Importantly, small doses of ibrutinib (0.1 muM) preserved the production of immunoregulatory IL-10 while effectively inhibiting hyperactivated, profibrotic effector B cells.	ibrutinib	28-37	interleukin 10	Homo sapiens	93-98
32228672-10	2020	In a flow cytometry analysis of phosphorylated NFkappaB, an important transcription factor in the induction of innate immune responses in B cells, significantly less activation was observed with ibrutinib treatment.	ibrutinib	195-204	nuclear factor kappa B subunit 1	Homo sapiens	47-55
32231778-2	2020	Inhibition of Bruton"s tyrosine kinase (BTK) has been a successful therapeutic strategy in CLL, and the first-generation BTK inhibitor ibrutinib has been shown to be superior to standard chemoimmunotherapy in multiple studies specifically targeting older patients.	ibrutinib	135-144	Bruton tyrosine kinase	Homo sapiens	121-124
32172299-4	2020	However, 17p-deleted, p53-mutated or IGHV-UM subgroups are generally resistant to FCR, and much better responses are seen with ibrutinib and venetoclax, frequently inducing MRD negativity that hopefully will be translated into durable remissions.	ibrutinib	127-136	tumor protein p53	Homo sapiens	22-25
32127472-4	2020	Loss of KLHL14 confers relative resistance to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and promotes assembly of the MYD88-TLR9-BCR (My-T-BCR) supercomplex, which initiates prosurvival NF-kappaB activation.	ibrutinib	89-98	kelch like family member 14	Homo sapiens	8-14
32127472-5	2020	Consequently, KLHL14 inactivation allows MCD cells to maintain NF-kappaB signaling in the presence of ibrutinib.	ibrutinib	102-111	kelch like family member 14	Homo sapiens	14-20
32014679-6	2020	Besides, combination of compound 5 and BTK inhibitor ibrutinib synergistically reduced the viability of TMD8 cells.	ibrutinib	53-62	Bruton tyrosine kinase	Homo sapiens	39-42
32172299-4	2020	However, 17p-deleted, p53-mutated or IGHV-UM subgroups are generally resistant to FCR, and much better responses are seen with ibrutinib and venetoclax, frequently inducing MRD negativity that hopefully will be translated into durable remissions.	ibrutinib	127-136	immunoglobulin heavy variable 3-69-1 (pseudogene)	Homo sapiens	37-41
32025027-1	2020	BACKGROUND: Ibrutinib is a Bruton"s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK) inhibitor used for treating chronic lymphocytic leukaemia (CLL) and other cancers.	ibrutinib	12-21	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	27-51
32168755-7	2020	ZAP-70+ is a surrogate for B cell receptor (BCR) activation and can be targeted by ibrutinib, which is a clinically approved Bruton"s tyrosine kinase (BTK) inhibitor.	ibrutinib	83-92	zeta chain of T cell receptor associated protein kinase 70	Homo sapiens	0-6
32168755-7	2020	ZAP-70+ is a surrogate for B cell receptor (BCR) activation and can be targeted by ibrutinib, which is a clinically approved Bruton"s tyrosine kinase (BTK) inhibitor.	ibrutinib	83-92	Bruton tyrosine kinase	Homo sapiens	125-149
32168755-7	2020	ZAP-70+ is a surrogate for B cell receptor (BCR) activation and can be targeted by ibrutinib, which is a clinically approved Bruton"s tyrosine kinase (BTK) inhibitor.	ibrutinib	83-92	Bruton tyrosine kinase	Homo sapiens	151-154
32168755-8	2020	Therefore, we evaluated the oxygen consumption rates (OCR) of CLL cells and plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4) levels from ibrutinib-treated patients and demonstrated decreased OCR similar to control B lymphocytes, suggesting that ibrutinib treatment resets the mitochondrial bioenergetics, while diminished CCL3/CCL4 levels indicate the down regulation of the BCR signaling pathway in CLL.	ibrutinib	145-154	C-C motif chemokine ligand 3	Homo sapiens	122-126
32168755-8	2020	Therefore, we evaluated the oxygen consumption rates (OCR) of CLL cells and plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4) levels from ibrutinib-treated patients and demonstrated decreased OCR similar to control B lymphocytes, suggesting that ibrutinib treatment resets the mitochondrial bioenergetics, while diminished CCL3/CCL4 levels indicate the down regulation of the BCR signaling pathway in CLL.	ibrutinib	145-154	C-C motif chemokine ligand 4	Homo sapiens	127-131
32168755-8	2020	Therefore, we evaluated the oxygen consumption rates (OCR) of CLL cells and plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4) levels from ibrutinib-treated patients and demonstrated decreased OCR similar to control B lymphocytes, suggesting that ibrutinib treatment resets the mitochondrial bioenergetics, while diminished CCL3/CCL4 levels indicate the down regulation of the BCR signaling pathway in CLL.	ibrutinib	145-154	C-C motif chemokine ligand 3	Homo sapiens	330-334
32168755-8	2020	Therefore, we evaluated the oxygen consumption rates (OCR) of CLL cells and plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4) levels from ibrutinib-treated patients and demonstrated decreased OCR similar to control B lymphocytes, suggesting that ibrutinib treatment resets the mitochondrial bioenergetics, while diminished CCL3/CCL4 levels indicate the down regulation of the BCR signaling pathway in CLL.	ibrutinib	145-154	C-C motif chemokine ligand 4	Homo sapiens	335-339
31316181-7	2020	Interestingly, the results of the kinase activity assay on a small panel of 35 kinases showed that the kinase selectivity of compound 2 was superior to that of the first-generation inhibitor ibrutinib, suggesting that compound 2 could be a second-generation inhibitor of BTK.	ibrutinib	191-200	Bruton tyrosine kinase	Homo sapiens	271-274
32239979-3	2020	When therapy is required, most patients will be treated with targeted therapies, either the Bruton tyrosine kinase (BTK) inhibitors ibrutinib or acalabrutinib or the BCL-2 inhibitor venetoclax in combination with obinutuzumab.	ibrutinib	132-141	Bruton tyrosine kinase	Homo sapiens	116-119
31682002-1	2020	Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Bruton"s tyrosine kinase inhibitor ibrutinib compared to younger patients.	ibrutinib	153-162	Bruton tyrosine kinase	Homo sapiens	118-142
31699465-1	2020	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is increasingly used in the treatment of chronic lymphocytic leukemia (CLL).	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	4-26
31699465-1	2020	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is increasingly used in the treatment of chronic lymphocytic leukemia (CLL).	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	28-31
32025027-1	2020	BACKGROUND: Ibrutinib is a Bruton"s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK) inhibitor used for treating chronic lymphocytic leukaemia (CLL) and other cancers.	ibrutinib	12-21	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	53-56
32025027-1	2020	BACKGROUND: Ibrutinib is a Bruton"s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK) inhibitor used for treating chronic lymphocytic leukaemia (CLL) and other cancers.	ibrutinib	12-21	IL2 inducible T cell kinase	Mus musculus	62-92
32025027-1	2020	BACKGROUND: Ibrutinib is a Bruton"s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK) inhibitor used for treating chronic lymphocytic leukaemia (CLL) and other cancers.	ibrutinib	12-21	IL2 inducible T cell kinase	Mus musculus	94-97
32025027-6	2020	We also confirmed that ex vivo treatment of MDSCs with ibrutinib switched their phenotype to mature DCs and significantly enhanced MHCII expression.	ibrutinib	55-64	histocompatibility-2, MHC	Mus musculus	131-136
32025027-7	2020	Further, ibrutinib treatment promoted T cell proliferation and effector functions leading to the induction of antitumour TH1 and CTL immune responses.	ibrutinib	9-18	negative elongation factor complex member C/D, Th1l	Mus musculus	121-124
31996046-4	2020	Since ibrutinib-resistant CLL clones can develop in about 20% of patients and toxicities, leading to drug discontinuation, occur in about 30% of patients treated with ibrutinib, several new BTK inhibitors have been developed in order to lower off-target effects and overcome ibrutinib resistance.Areas covered: In this review, we summarize the main English publications exploring efficacy and side effects of first and next-generation BTK inhibitors.	ibrutinib	6-15	Bruton tyrosine kinase	Homo sapiens	190-193
31664782-1	2020	The oral bioavailability of ibrutinib is low and variable, mainly due to extensive first-pass metabolism by CYP3A4.	ibrutinib	28-37	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	108-114
31996046-4	2020	Since ibrutinib-resistant CLL clones can develop in about 20% of patients and toxicities, leading to drug discontinuation, occur in about 30% of patients treated with ibrutinib, several new BTK inhibitors have been developed in order to lower off-target effects and overcome ibrutinib resistance.Areas covered: In this review, we summarize the main English publications exploring efficacy and side effects of first and next-generation BTK inhibitors.	ibrutinib	167-176	Bruton tyrosine kinase	Homo sapiens	190-193
31996046-4	2020	Since ibrutinib-resistant CLL clones can develop in about 20% of patients and toxicities, leading to drug discontinuation, occur in about 30% of patients treated with ibrutinib, several new BTK inhibitors have been developed in order to lower off-target effects and overcome ibrutinib resistance.Areas covered: In this review, we summarize the main English publications exploring efficacy and side effects of first and next-generation BTK inhibitors.	ibrutinib	167-176	Bruton tyrosine kinase	Homo sapiens	190-193
31996046-5	2020	Results of clinical trials evaluating these novel agents are presented and critically discussed.Expert opinion: Efforts in the development of highly specific second-generation BTK inhibitors and combination strategies provide challenging options to overcome limitations of therapy with ibrutinib.	ibrutinib	286-295	Bruton tyrosine kinase	Homo sapiens	176-179
31996046-0	2020	Emerging bruton tyrosine kinase inhibitors for chronic lymphocytic leukaemia: one step ahead ibrutinib.	ibrutinib	93-102	Bruton tyrosine kinase	Homo sapiens	9-31
31871305-3	2020	To illustrate this concept, we assessed the selectivity of Bruton"s tyrosine kinase (BTK) over TEC kinases by two novel therapeutics: ibrutinib and acalabrutinib.	ibrutinib	134-143	Bruton tyrosine kinase	Homo sapiens	59-83
31996046-2	2020	As matter of fact, ibrutinib, the first-in-class Bruton tyrosine kinase (BTK) inhibitor, became a milestone in the treatment of both naive or relapsed/refractory CLL patients.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	49-71
31996046-2	2020	As matter of fact, ibrutinib, the first-in-class Bruton tyrosine kinase (BTK) inhibitor, became a milestone in the treatment of both naive or relapsed/refractory CLL patients.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	73-76
31982823-5	2020	In the present study, we investigated the effect of selective BTK inhibitor, PCI-32765 on inflammatory signaling in CD11c + DCs and gamma delta T cells in imiquimod (IMQ)-induced mouse model of psoriasis-like inflammation.	ibrutinib	77-86	integrin subunit alpha X	Homo sapiens	116-121
31871305-3	2020	To illustrate this concept, we assessed the selectivity of Bruton"s tyrosine kinase (BTK) over TEC kinases by two novel therapeutics: ibrutinib and acalabrutinib.	ibrutinib	134-143	Bruton tyrosine kinase	Homo sapiens	85-88
31871305-3	2020	To illustrate this concept, we assessed the selectivity of Bruton"s tyrosine kinase (BTK) over TEC kinases by two novel therapeutics: ibrutinib and acalabrutinib.	ibrutinib	134-143	tec protein tyrosine kinase	Homo sapiens	95-98
31871305-5	2020	The selectivity for BTK over TEC found in these biochemical analyses was 1-1.5 for ibrutinib and 3.0-4.2 for acalabrutinib.	ibrutinib	83-92	Bruton tyrosine kinase	Homo sapiens	20-23
31871305-5	2020	The selectivity for BTK over TEC found in these biochemical analyses was 1-1.5 for ibrutinib and 3.0-4.2 for acalabrutinib.	ibrutinib	83-92	tec protein tyrosine kinase	Homo sapiens	29-32
31871305-8	2020	In MWCL-1 cells, BTK/TEC selectivities measured at 0.5, 1, and 3 hours were 2.53, 1.05, and 1.51 for ibrutinib and 0.97, 1.13, and 2.56 for acalabrutinib, respectively.	ibrutinib	101-110	Bruton tyrosine kinase	Homo sapiens	17-20
31871305-8	2020	In MWCL-1 cells, BTK/TEC selectivities measured at 0.5, 1, and 3 hours were 2.53, 1.05, and 1.51 for ibrutinib and 0.97, 1.13, and 2.56 for acalabrutinib, respectively.	ibrutinib	101-110	tec protein tyrosine kinase	Homo sapiens	21-24
31871305-10	2020	Collectively, our data show that when properly accounting for time-dependent factors and relevant cellular context, ibrutinib and acalabrutinib demonstrate similar selectivity for BTK over TEC.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	180-183
31871305-10	2020	Collectively, our data show that when properly accounting for time-dependent factors and relevant cellular context, ibrutinib and acalabrutinib demonstrate similar selectivity for BTK over TEC.	ibrutinib	116-125	tec protein tyrosine kinase	Homo sapiens	189-192
31628428-4	2020	Ibrutinib benefit was also consistent in patients with high prognostic risk (TP53 mutation, 11q deletion, and/or unmutated IGHV) (PFS: HR [95% CI]: 0.083 [0.047-0.145]; OS: HR [95% CI]: 0.366 [0.181-0.736]).	ibrutinib	0-9	tumor protein p53	Homo sapiens	77-81
31628428-4	2020	Ibrutinib benefit was also consistent in patients with high prognostic risk (TP53 mutation, 11q deletion, and/or unmutated IGHV) (PFS: HR [95% CI]: 0.083 [0.047-0.145]; OS: HR [95% CI]: 0.366 [0.181-0.736]).	ibrutinib	0-9	immunoglobulin heavy variable 3-69-1 (pseudogene)	Homo sapiens	123-127
32006301-4	2020	The success of the first-generation Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has generated tremendous interest in the study of more selective and potent BTK inhibitors.	ibrutinib	76-85	Bruton tyrosine kinase	Homo sapiens	36-58
32186759-0	2020	PDGFD induces ibrutinib resistance of diffuse large B-cell lymphoma through activation of EGFR.	ibrutinib	14-23	platelet derived growth factor D	Homo sapiens	0-5
32186759-0	2020	PDGFD induces ibrutinib resistance of diffuse large B-cell lymphoma through activation of EGFR.	ibrutinib	14-23	epidermal growth factor receptor	Homo sapiens	90-94
32186759-1	2020	Ibrutinib, an FDA approved, orally administered BTK inhibitor, has demonstrated high response rates to diffuse large B-cell lymphoma (DLBCL), however, complete responses are infrequent and acquired resistance to BTK inhibition can emerge.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	48-51
32186759-1	2020	Ibrutinib, an FDA approved, orally administered BTK inhibitor, has demonstrated high response rates to diffuse large B-cell lymphoma (DLBCL), however, complete responses are infrequent and acquired resistance to BTK inhibition can emerge.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	212-215
32186759-6	2020	The expression of PDGFD in tissues that were resistant or susceptible to DLBCL/ibrutinib was detected via immunohistochemistry (IHC), and the expression of PDGFD in DLBCL/ibrutinib-resistant strains and their parental counterparts were examined via reverse transcription-quantitative PCR and western blot analyses.	ibrutinib	79-88	platelet derived growth factor D	Homo sapiens	18-23
32186759-6	2020	The expression of PDGFD in tissues that were resistant or susceptible to DLBCL/ibrutinib was detected via immunohistochemistry (IHC), and the expression of PDGFD in DLBCL/ibrutinib-resistant strains and their parental counterparts were examined via reverse transcription-quantitative PCR and western blot analyses.	ibrutinib	171-180	platelet derived growth factor D	Homo sapiens	156-161
32186759-7	2020	Subsequently, a drug-resistant cell model of DLBCL/ibrutinib in which PDGFD was silenced was constructed.	ibrutinib	51-60	platelet derived growth factor D	Homo sapiens	70-75
32186759-13	2020	The interaction network diagram showed that there was a regulatory relationship between PDGFD and disease-related genes, and that PDGFD could indirectly target the ibrutinib target gene EGFR, indicating that PDGFD could regulate DLBCL via EGFR.	ibrutinib	164-173	platelet derived growth factor D	Homo sapiens	130-135
32186759-13	2020	The interaction network diagram showed that there was a regulatory relationship between PDGFD and disease-related genes, and that PDGFD could indirectly target the ibrutinib target gene EGFR, indicating that PDGFD could regulate DLBCL via EGFR.	ibrutinib	164-173	epidermal growth factor receptor	Homo sapiens	186-190
32186759-13	2020	The interaction network diagram showed that there was a regulatory relationship between PDGFD and disease-related genes, and that PDGFD could indirectly target the ibrutinib target gene EGFR, indicating that PDGFD could regulate DLBCL via EGFR.	ibrutinib	164-173	platelet derived growth factor D	Homo sapiens	130-135
32186759-13	2020	The interaction network diagram showed that there was a regulatory relationship between PDGFD and disease-related genes, and that PDGFD could indirectly target the ibrutinib target gene EGFR, indicating that PDGFD could regulate DLBCL via EGFR.	ibrutinib	164-173	epidermal growth factor receptor	Homo sapiens	239-243
32186759-14	2020	IHC results showed high expression of PDGFD in diffuse large B-cell lymphoma tissues with ibrutinib tolerance.	ibrutinib	90-99	platelet derived growth factor D	Homo sapiens	38-43
32186759-15	2020	PDGFD expression in ibrutinib-resistant DLBCL cells was higher compared with in parental cells.	ibrutinib	20-29	platelet derived growth factor D	Homo sapiens	0-5
32186759-16	2020	Following interference with PDGFD expression in ibrutinib-resistant DLBCL cells, the IC50 value of ibrutinib decreased, the rate of apoptosis increased and EGFR expression decreased.	ibrutinib	48-57	platelet derived growth factor D	Homo sapiens	28-33
32186759-16	2020	Following interference with PDGFD expression in ibrutinib-resistant DLBCL cells, the IC50 value of ibrutinib decreased, the rate of apoptosis increased and EGFR expression decreased.	ibrutinib	48-57	epidermal growth factor receptor	Homo sapiens	156-160
32186759-16	2020	Following interference with PDGFD expression in ibrutinib-resistant DLBCL cells, the IC50 value of ibrutinib decreased, the rate of apoptosis increased and EGFR expression decreased.	ibrutinib	99-108	platelet derived growth factor D	Homo sapiens	28-33
32186759-17	2020	In brief, EGFR overexpression can reverse the resistance of DLBCL to ibrutinib via PDGFD interference, and PDGFD induces the resistance of DLBCL to ibrutinib via EGFR.	ibrutinib	69-78	epidermal growth factor receptor	Homo sapiens	10-14
32186759-17	2020	In brief, EGFR overexpression can reverse the resistance of DLBCL to ibrutinib via PDGFD interference, and PDGFD induces the resistance of DLBCL to ibrutinib via EGFR.	ibrutinib	69-78	platelet derived growth factor D	Homo sapiens	83-88
32110454-3	2020	Ibrutinib is a Bruton"s tyrosine kinase (BTK) inhibitor approved for the treatment of several hematologic malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	15-39
32110454-3	2020	Ibrutinib is a Bruton"s tyrosine kinase (BTK) inhibitor approved for the treatment of several hematologic malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	41-44
32110454-8	2020	In the case of ibrutinib, the off-target effects on EGFR, c-kit, and platelet-derived growth factor receptor (PDGFR) are thought to be responsible for the cutaneous eruption of various forms of rash.	ibrutinib	15-24	epidermal growth factor	Homo sapiens	52-56
32110454-8	2020	In the case of ibrutinib, the off-target effects on EGFR, c-kit, and platelet-derived growth factor receptor (PDGFR) are thought to be responsible for the cutaneous eruption of various forms of rash.	ibrutinib	15-24	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	58-63
32110454-8	2020	In the case of ibrutinib, the off-target effects on EGFR, c-kit, and platelet-derived growth factor receptor (PDGFR) are thought to be responsible for the cutaneous eruption of various forms of rash.	ibrutinib	15-24	platelet derived growth factor receptor beta	Homo sapiens	69-108
32110454-8	2020	In the case of ibrutinib, the off-target effects on EGFR, c-kit, and platelet-derived growth factor receptor (PDGFR) are thought to be responsible for the cutaneous eruption of various forms of rash.	ibrutinib	15-24	platelet derived growth factor receptor beta	Homo sapiens	110-115
32006301-4	2020	The success of the first-generation Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has generated tremendous interest in the study of more selective and potent BTK inhibitors.	ibrutinib	76-85	Bruton tyrosine kinase	Homo sapiens	60-63
31924585-2	2020	Although recently introduced small-molecule B-cell receptor signalling inhibitors have revolutionized CLL treatment, data for ibrutinib still point to impaired prognosis for TP53-affected patients.	ibrutinib	126-135	tumor protein p53	Homo sapiens	174-178
31772331-6	2020	Furthermore, its killing efficacy rose on combination with venetoclax, the BCL-XL-specific inhibitor A-1331852, or Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, which reduced pro-survival signals.	ibrutinib	156-165	Bruton tyrosine kinase	Homo sapiens	115-139
31582534-0	2020	Ibrutinib potentiates anti-hepatocarcinogenic efficacy of sorafenib by targeting EGFR in tumor cells and BTK in immune cells in the stroma.	ibrutinib	0-9	epidermal growth factor receptor	Mus musculus	81-85
31582534-3	2020	Ibrutinib, an irreversible tyrosine kinase inhibitor (TKI) of TEC (e.g. BTK) and ErbB (e.g. EGFR) families, is an approved treatment for B cell malignancies.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	72-75
31582534-3	2020	Ibrutinib, an irreversible tyrosine kinase inhibitor (TKI) of TEC (e.g. BTK) and ErbB (e.g. EGFR) families, is an approved treatment for B cell malignancies.	ibrutinib	0-9	epidermal growth factor receptor	Mus musculus	81-85
31582534-3	2020	Ibrutinib, an irreversible tyrosine kinase inhibitor (TKI) of TEC (e.g. BTK) and ErbB (e.g. EGFR) families, is an approved treatment for B cell malignancies.	ibrutinib	0-9	epidermal growth factor receptor	Mus musculus	92-96
31582534-5	2020	Mechanistically, ibrutinib inactivated EGFR and its downstream Akt and ERK signaling in HCC cells, and downregulated a set of critical genes involved in cell proliferation, migration, survival and stemness, and upregulated genes promoting differentiation.	ibrutinib	17-26	epidermal growth factor receptor	Mus musculus	39-43
31582534-5	2020	Mechanistically, ibrutinib inactivated EGFR and its downstream Akt and ERK signaling in HCC cells, and downregulated a set of critical genes involved in cell proliferation, migration, survival and stemness, and upregulated genes promoting differentiation.	ibrutinib	17-26	thymoma viral proto-oncogene 1	Mus musculus	63-66
31582534-5	2020	Mechanistically, ibrutinib inactivated EGFR and its downstream Akt and ERK signaling in HCC cells, and downregulated a set of critical genes involved in cell proliferation, migration, survival and stemness, and upregulated genes promoting differentiation.	ibrutinib	17-26	Eph receptor B2	Mus musculus	71-74
31582534-8	2020	In immune competent mice, the ibrutinib-sorafenib combination reduced the numbers of BTK+ immune cells in the tumor microenvironment.	ibrutinib	30-49	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	85-88
31582534-10	2020	Collectively, our findings implicate BTK signaling in hepatocarcinogenesis and support clinical trials of the sorafenib-ibrutinib combination for this deadly disease.	ibrutinib	110-129	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	37-40
31772331-6	2020	Furthermore, its killing efficacy rose on combination with venetoclax, the BCL-XL-specific inhibitor A-1331852, or Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, which reduced pro-survival signals.	ibrutinib	156-165	Bruton tyrosine kinase	Homo sapiens	141-144
31772331-10	2020	Accordingly, sensitivity of the CD40L-stimulated cells to S63845 was substantially restored by co-treatment with venetoclax, the BCL-XL-specific inhibitor or ibrutinib.	ibrutinib	158-167	CD40 ligand	Homo sapiens	32-37
31986467-6	2020	It was showed that the related protein expression of reactive oxygen species (ROS) in the ibrutinib group was significantly increased, including NOX2, NOX4, p22-phox, XO and TGF-beta protein expression.	ibrutinib	90-99	cytochrome b-245, beta polypeptide	Mus musculus	145-149
31986467-6	2020	It was showed that the related protein expression of reactive oxygen species (ROS) in the ibrutinib group was significantly increased, including NOX2, NOX4, p22-phox, XO and TGF-beta protein expression.	ibrutinib	90-99	NADPH oxidase 4	Mus musculus	151-155
31986467-6	2020	It was showed that the related protein expression of reactive oxygen species (ROS) in the ibrutinib group was significantly increased, including NOX2, NOX4, p22-phox, XO and TGF-beta protein expression.	ibrutinib	90-99	dynein cytoplasmic 1 heavy chain 1	Mus musculus	157-160
31986467-6	2020	It was showed that the related protein expression of reactive oxygen species (ROS) in the ibrutinib group was significantly increased, including NOX2, NOX4, p22-phox, XO and TGF-beta protein expression.	ibrutinib	90-99	transforming growth factor alpha	Mus musculus	174-182
31986467-7	2020	It was interesting that ibrutinib group also significantly increased the expression of ox-CaMKII, p-CaMKII (Thr-286) and p-RyR2 (Ser2814), causing enhanced abnormal sarcoplasmic reticulum (SR) Ca2+ release and mitochondrial structures, as well as atrial fibrosis and atrial hypertrophy in ibrutinib-treated mice, and apocynin reduced the expression of these proteins.	ibrutinib	24-33	ryanodine receptor 2, cardiac	Mus musculus	123-127
31414181-1	2020	Ibrutinib is the first clinically approved inhibitor of Bruton"s tyrosine kinase, an enzyme that is essential for survival and proliferation of B-cells by activating the B-cell receptor signalling pathway.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	56-80
32005797-1	2020	Activating MYD88 mutations promote pro-survival signaling through BTK and HCK, both targets of ibrutinib.	ibrutinib	95-104	MYD88 innate immune signal transduction adaptor	Homo sapiens	11-16
32005797-1	2020	Activating MYD88 mutations promote pro-survival signaling through BTK and HCK, both targets of ibrutinib.	ibrutinib	95-104	Bruton tyrosine kinase	Homo sapiens	66-69
32005797-1	2020	Activating MYD88 mutations promote pro-survival signaling through BTK and HCK, both targets of ibrutinib.	ibrutinib	95-104	HCK proto-oncogene, Src family tyrosine kinase	Homo sapiens	74-77
32005797-8	2020	Cell viability analysis showed that combining ibrutinib and SYK inhibitors triggered synthetic killing of MYD88-mutated lymphoma cells.	ibrutinib	46-55	MYD88 innate immune signal transduction adaptor	Homo sapiens	106-111
32005797-10	2020	Targeting SYK in combination with ibrutinib produces synthetic lethality, providing a framework for the clinical investigation of ibrutinib with SYK inhibitors in MYD88-mutated lymphomas.	ibrutinib	130-139	spleen associated tyrosine kinase	Homo sapiens	10-13
32027299-4	2020	Currently, BTK inhibitors developed include the first-generation Ibrutinib and the second-generation Acalabrutinib, which can be targeted at the inhibition of BTK and its downstream signaling pathway, and have important therapeutic value for a variety of B-cell tumors, such as CLL and partial non-Hodgkin"s lymphoma (NHL).	ibrutinib	65-74	Bruton tyrosine kinase	Homo sapiens	11-14
32027299-4	2020	Currently, BTK inhibitors developed include the first-generation Ibrutinib and the second-generation Acalabrutinib, which can be targeted at the inhibition of BTK and its downstream signaling pathway, and have important therapeutic value for a variety of B-cell tumors, such as CLL and partial non-Hodgkin"s lymphoma (NHL).	ibrutinib	65-74	Bruton tyrosine kinase	Homo sapiens	159-162
31171645-0	2020	Differential effects of BTK inhibitors ibrutinib and zanubrutinib on NK cell effector function in patients with mantle cell lymphoma.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	24-27
31996669-1	2020	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for patients with chronic lymphocytic leukemia (CLL), despite extensive heterogeneity in this disease.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	4-26
31996669-1	2020	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for patients with chronic lymphocytic leukemia (CLL), despite extensive heterogeneity in this disease.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	28-31
31736210-6	2020	Here, we show that ibrutinib, a clinically approved covalent inhibitor of BTK, prolonged the maximum lifespan of a Zmpste24-/- progeroid mice, which also showed a reduction in general age-related fitness loss.	ibrutinib	19-28	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	74-77
31736210-6	2020	Here, we show that ibrutinib, a clinically approved covalent inhibitor of BTK, prolonged the maximum lifespan of a Zmpste24-/- progeroid mice, which also showed a reduction in general age-related fitness loss.	ibrutinib	19-28	zinc metallopeptidase, STE24	Mus musculus	115-123
32075387-10	2020	Interestingly, STAT3 inhibition was disclosed as an important by-product of ibrutinib treatment in CLL patients.	ibrutinib	76-85	signal transducer and activator of transcription 3	Homo sapiens	15-20
31811349-12	2020	With the application of ibrutinib, the selective inhibitor of BTK, it was also found that BTK/TLR4/NF-kappaB pathway was associated with the GEN treatment in high glucose-induced SH-SY5Y cells.	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	62-65
31811349-12	2020	With the application of ibrutinib, the selective inhibitor of BTK, it was also found that BTK/TLR4/NF-kappaB pathway was associated with the GEN treatment in high glucose-induced SH-SY5Y cells.	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	90-93
31811349-12	2020	With the application of ibrutinib, the selective inhibitor of BTK, it was also found that BTK/TLR4/NF-kappaB pathway was associated with the GEN treatment in high glucose-induced SH-SY5Y cells.	ibrutinib	24-33	toll like receptor 4	Homo sapiens	94-98
31811349-12	2020	With the application of ibrutinib, the selective inhibitor of BTK, it was also found that BTK/TLR4/NF-kappaB pathway was associated with the GEN treatment in high glucose-induced SH-SY5Y cells.	ibrutinib	24-33	nuclear factor kappa B subunit 1	Homo sapiens	99-108
31676420-4	2020	An increase in the incidence of opportunistic fungal infections was recently reported in patients with hematological cancers receiving treatment with the BTK inhibitor, Ibrutinib.	ibrutinib	169-178	Bruton tyrosine kinase	Homo sapiens	154-157
31180577-1	2020	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
31180577-1	2020	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
31180577-1	2020	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance.	ibrutinib	45-54	tumor protein p53	Homo sapiens	173-177
31180577-1	2020	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	191-194
31180577-1	2020	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance.	ibrutinib	45-54	phospholipase C gamma 2	Homo sapiens	199-222
31180577-1	2020	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance.	ibrutinib	45-54	phospholipase C gamma 2	Homo sapiens	224-229
31180577-1	2020	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance.	ibrutinib	302-311	Bruton tyrosine kinase	Homo sapiens	4-28
31180577-1	2020	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance.	ibrutinib	302-311	Bruton tyrosine kinase	Homo sapiens	30-33
31180577-3	2020	Mutations in the SF3B1, MGAand BIRC3 genes were enriched during ibrutinib treatment, while aberrations in the BTK, PLCG2, RIPK1, NFKBIE and XPO1 genes were exclusively detected in posttreatment samples.	ibrutinib	64-73	splicing factor 3b subunit 1	Homo sapiens	17-22
31180577-3	2020	Mutations in the SF3B1, MGAand BIRC3 genes were enriched during ibrutinib treatment, while aberrations in the BTK, PLCG2, RIPK1, NFKBIE and XPO1 genes were exclusively detected in posttreatment samples.	ibrutinib	64-73	baculoviral IAP repeat containing 3	Homo sapiens	31-36
31180577-7	2020	In conclusion, subclonal heterogeneity, dynamic clonal selection and various patterns of clonal variegation were identified with novel resistance-associated BTK mutations in individual patients treated with ibrutinib.	ibrutinib	207-216	Bruton tyrosine kinase	Homo sapiens	157-160
31216242-1	2020	INTRODUCTION: Ibrutinib is an oral inhibitor of Bruton"s tyrosine kinase that is used for a variety of B cell hematological malignancies.	ibrutinib	14-23	Bruton tyrosine kinase	Homo sapiens	48-72
31216242-3	2020	The mechanism in which ibrutinib can cause skin toxicities has been thought due to the inhibition of epidermal growth factor; c-Kit and platelet-derived growth factor receptor).	ibrutinib	23-32	epidermal growth factor	Homo sapiens	101-124
31216242-3	2020	The mechanism in which ibrutinib can cause skin toxicities has been thought due to the inhibition of epidermal growth factor; c-Kit and platelet-derived growth factor receptor).	ibrutinib	23-32	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	126-131
33188997-4	2020	A quantitative assay evaluated Bruton"s tyrosine kinase (BTK) occupancy by ibrutinib in peripheral blood mononuclear cells.	ibrutinib	75-84	Bruton tyrosine kinase	Homo sapiens	31-55
33188997-4	2020	A quantitative assay evaluated Bruton"s tyrosine kinase (BTK) occupancy by ibrutinib in peripheral blood mononuclear cells.	ibrutinib	75-84	Bruton tyrosine kinase	Homo sapiens	57-60
31726100-0	2020	Destabilization of ROR1 enhances activity of Ibrutinib against chronic lymphocytic leukemia in vivo.	ibrutinib	45-54	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	19-23
31357193-1	2020	BACKGROUND: Ibrutinib is an orally administered inhibitor of Bruton"s tyrosine kinase (Btk).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	61-85
31357193-1	2020	BACKGROUND: Ibrutinib is an orally administered inhibitor of Bruton"s tyrosine kinase (Btk).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	87-90
31726100-5	2020	Based on our previous finding that a humanized monoclonal antibody against ROR1 increases the activity of Ibrutinib against CLL, which is currently undergoing evaluation in clinical trials for the treatment of B-cell lymphoid malignancies, we then provided evidence that treatment with HSP90 inhibitor (17-DMAG) enhances anti-CLL activity of Ibrutinib in vitro and in vivo, by down-modulating ROR1.	ibrutinib	106-115	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	75-79
31726100-5	2020	Based on our previous finding that a humanized monoclonal antibody against ROR1 increases the activity of Ibrutinib against CLL, which is currently undergoing evaluation in clinical trials for the treatment of B-cell lymphoid malignancies, we then provided evidence that treatment with HSP90 inhibitor (17-DMAG) enhances anti-CLL activity of Ibrutinib in vitro and in vivo, by down-modulating ROR1.	ibrutinib	106-115	heat shock protein 90 alpha family class A member 1	Homo sapiens	286-291
31726100-5	2020	Based on our previous finding that a humanized monoclonal antibody against ROR1 increases the activity of Ibrutinib against CLL, which is currently undergoing evaluation in clinical trials for the treatment of B-cell lymphoid malignancies, we then provided evidence that treatment with HSP90 inhibitor (17-DMAG) enhances anti-CLL activity of Ibrutinib in vitro and in vivo, by down-modulating ROR1.	ibrutinib	106-115	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	393-397
31726100-5	2020	Based on our previous finding that a humanized monoclonal antibody against ROR1 increases the activity of Ibrutinib against CLL, which is currently undergoing evaluation in clinical trials for the treatment of B-cell lymphoid malignancies, we then provided evidence that treatment with HSP90 inhibitor (17-DMAG) enhances anti-CLL activity of Ibrutinib in vitro and in vivo, by down-modulating ROR1.	ibrutinib	342-351	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	75-79
31726100-7	2020	However, immunoblotting validation confirmed that Ibrutinib treatment dramatically deprived HSP90 inhibitors, 17-DMAG, AUY922 or PU-H71, of inducing the degradation of BTK, BLK, LCK or LYN, but not ROR1.	ibrutinib	50-59	heat shock protein 90 alpha family class A member 1	Homo sapiens	92-97
31726100-7	2020	However, immunoblotting validation confirmed that Ibrutinib treatment dramatically deprived HSP90 inhibitors, 17-DMAG, AUY922 or PU-H71, of inducing the degradation of BTK, BLK, LCK or LYN, but not ROR1.	ibrutinib	50-59	Bruton tyrosine kinase	Homo sapiens	168-171
31726100-7	2020	However, immunoblotting validation confirmed that Ibrutinib treatment dramatically deprived HSP90 inhibitors, 17-DMAG, AUY922 or PU-H71, of inducing the degradation of BTK, BLK, LCK or LYN, but not ROR1.	ibrutinib	50-59	BLK proto-oncogene, Src family tyrosine kinase	Homo sapiens	173-176
31726100-7	2020	However, immunoblotting validation confirmed that Ibrutinib treatment dramatically deprived HSP90 inhibitors, 17-DMAG, AUY922 or PU-H71, of inducing the degradation of BTK, BLK, LCK or LYN, but not ROR1.	ibrutinib	50-59	LCK proto-oncogene, Src family tyrosine kinase	Homo sapiens	178-181
31726100-7	2020	However, immunoblotting validation confirmed that Ibrutinib treatment dramatically deprived HSP90 inhibitors, 17-DMAG, AUY922 or PU-H71, of inducing the degradation of BTK, BLK, LCK or LYN, but not ROR1.	ibrutinib	50-59	LYN proto-oncogene, Src family tyrosine kinase	Homo sapiens	185-188
31726100-7	2020	However, immunoblotting validation confirmed that Ibrutinib treatment dramatically deprived HSP90 inhibitors, 17-DMAG, AUY922 or PU-H71, of inducing the degradation of BTK, BLK, LCK or LYN, but not ROR1.	ibrutinib	50-59	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	198-202
31726100-8	2020	Collectively, our data suggested that depletion of ROR1 induced by targeting HSP90 might facilitate the enhancement of Ibrutinib activity against CLL.	ibrutinib	119-128	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	51-55
31726100-8	2020	Collectively, our data suggested that depletion of ROR1 induced by targeting HSP90 might facilitate the enhancement of Ibrutinib activity against CLL.	ibrutinib	119-128	heat shock protein 90 alpha family class A member 1	Homo sapiens	77-82
31869418-1	2019	The Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib has proven to be efficacious in the treatment of B-cell chronic lymphocytic leukemia (B-CLL) and related diseases.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
31869418-7	2019	Ibrutinib but not zanubrutinib treatment of human platelets increased ADAM17 activation.	ibrutinib	0-9	ADAM metallopeptidase domain 17	Homo sapiens	70-76
31869418-1	2019	The Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib has proven to be efficacious in the treatment of B-cell chronic lymphocytic leukemia (B-CLL) and related diseases.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
31869418-3	2019	The bleeding associated with ibrutinib use is thought to be due to a combination of on-target irreversible Btk inhibition, as well as off-target inhibition of other kinases, including EGFR, ITK, JAK3, and Tec kinase.	ibrutinib	29-38	Bruton tyrosine kinase	Homo sapiens	107-110
31869418-10	2019	In mice, ibrutinib, but not zanubrutinib, led to increased soluble GPIbalpha and soluble alphaIIb levels in plasma.	ibrutinib	9-18	glycoprotein 1b, alpha polypeptide	Mus musculus	67-76
31869418-3	2019	The bleeding associated with ibrutinib use is thought to be due to a combination of on-target irreversible Btk inhibition, as well as off-target inhibition of other kinases, including EGFR, ITK, JAK3, and Tec kinase.	ibrutinib	29-38	epidermal growth factor receptor	Homo sapiens	184-188
31869418-3	2019	The bleeding associated with ibrutinib use is thought to be due to a combination of on-target irreversible Btk inhibition, as well as off-target inhibition of other kinases, including EGFR, ITK, JAK3, and Tec kinase.	ibrutinib	29-38	IL2 inducible T cell kinase	Homo sapiens	190-193
31869418-10	2019	In mice, ibrutinib, but not zanubrutinib, led to increased soluble GPIbalpha and soluble alphaIIb levels in plasma.	ibrutinib	9-18	adrenergic receptor, alpha 2b	Mus musculus	89-97
31869418-3	2019	The bleeding associated with ibrutinib use is thought to be due to a combination of on-target irreversible Btk inhibition, as well as off-target inhibition of other kinases, including EGFR, ITK, JAK3, and Tec kinase.	ibrutinib	29-38	Janus kinase 3	Homo sapiens	195-199
31869418-11	2019	These data demonstrate that ibrutinib induces shedding of GPIbalpha and GPIX by an ADAM17-dependent mechanism and integrin alphaIIbbeta3 by an unknown sheddase, and this process occurs in vivo to regulate thrombus formation.	ibrutinib	28-37	glycoprotein Ib platelet subunit alpha	Homo sapiens	58-67
31743002-4	2019	By using the specific antibody, we not only confirm the well-known ibrutinib-binding target BTK, but also identify some previously undescribed strongly binding proteins, such as CKAP4 in human cell lines, and TAP1 in mouse organs.	ibrutinib	67-76	Bruton tyrosine kinase	Homo sapiens	92-95
31869418-11	2019	These data demonstrate that ibrutinib induces shedding of GPIbalpha and GPIX by an ADAM17-dependent mechanism and integrin alphaIIbbeta3 by an unknown sheddase, and this process occurs in vivo to regulate thrombus formation.	ibrutinib	28-37	glycoprotein IX platelet	Homo sapiens	72-76
31869418-11	2019	These data demonstrate that ibrutinib induces shedding of GPIbalpha and GPIX by an ADAM17-dependent mechanism and integrin alphaIIbbeta3 by an unknown sheddase, and this process occurs in vivo to regulate thrombus formation.	ibrutinib	28-37	ADAM metallopeptidase domain 17	Homo sapiens	83-89
31861854-4	2019	Ibrutinib, the first-in-class BTKi, also inhibits Tec family kinases such as interleukin-2-inducible kinase (ITK), a proximal member of the T-cell receptor signaling cascade.	ibrutinib	0-9	inhibitor of Bruton tyrosine kinase	Homo sapiens	30-34
31861854-4	2019	Ibrutinib, the first-in-class BTKi, also inhibits Tec family kinases such as interleukin-2-inducible kinase (ITK), a proximal member of the T-cell receptor signaling cascade.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	77-107
31861854-4	2019	Ibrutinib, the first-in-class BTKi, also inhibits Tec family kinases such as interleukin-2-inducible kinase (ITK), a proximal member of the T-cell receptor signaling cascade.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	109-112
31870917-0	2019	Cutaneous Eruptions from Ibrutinib Resembling EGFR Inhibitor-Induced Dermatologic Adverse Events.	ibrutinib	25-34	epidermal growth factor receptor	Homo sapiens	46-50
31870917-1	2019	BACKGROUND: Ibrutinib is an oral inhibitor of Bruton"s tyrosine kinase (BTK) that is FDA-approved for several lymphoproliferative disorders and chronic GVHD.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	46-70
31870917-1	2019	BACKGROUND: Ibrutinib is an oral inhibitor of Bruton"s tyrosine kinase (BTK) that is FDA-approved for several lymphoproliferative disorders and chronic GVHD.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	72-75
31870917-7	2019	CONCLUSIONS: With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors.	ibrutinib	74-83	epidermal growth factor receptor	Homo sapiens	129-133
31743002-4	2019	By using the specific antibody, we not only confirm the well-known ibrutinib-binding target BTK, but also identify some previously undescribed strongly binding proteins, such as CKAP4 in human cell lines, and TAP1 in mouse organs.	ibrutinib	67-76	cytoskeleton associated protein 4	Homo sapiens	178-183
31743002-4	2019	By using the specific antibody, we not only confirm the well-known ibrutinib-binding target BTK, but also identify some previously undescribed strongly binding proteins, such as CKAP4 in human cell lines, and TAP1 in mouse organs.	ibrutinib	67-76	transporter 1, ATP binding cassette subfamily B member	Homo sapiens	209-213
31578228-0	2019	Decreased NOTCH1 Activation Correlates with Response to Ibrutinib in Chronic Lymphocytic Leukemia.	ibrutinib	56-65	notch receptor 1	Homo sapiens	10-16
31578228-1	2019	PURPOSE: Ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), has improved the outcomes of chronic lymphocytic leukemia (CLL), but primary resistance or relapse are issues of increasing significance.	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	22-44
31578228-8	2019	Results of in situ PLA experiments revealed the presence of NOTCH1-ICD/BTK complexes, whose number was reduced after ibrutinib treatment.	ibrutinib	117-126	notch receptor 1	Homo sapiens	60-66
31578228-1	2019	PURPOSE: Ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), has improved the outcomes of chronic lymphocytic leukemia (CLL), but primary resistance or relapse are issues of increasing significance.	ibrutinib	9-18	inhibitor of Bruton tyrosine kinase	Homo sapiens	56-60
31578228-8	2019	Results of in situ PLA experiments revealed the presence of NOTCH1-ICD/BTK complexes, whose number was reduced after ibrutinib treatment.	ibrutinib	117-126	Bruton tyrosine kinase	Homo sapiens	71-74
31578228-9	2019	In ibrutinib-treated CLL patients, leukemic cells showed NOTCH1 activity downregulation that deepened over time.	ibrutinib	3-12	notch receptor 1	Homo sapiens	57-63
31578228-3	2019	We investigated potential interactions between BCR pathway and NOTCH1 activity in ibrutinib-treated CLL to identify new mechanisms of therapy resistance and markers to monitor disease response.	ibrutinib	82-91	notch receptor 1	Homo sapiens	63-69
31578228-10	2019	The NOTCH1 signaling was restored at relapse and remained activated in ibrutinib-resistant CLL cells.	ibrutinib	71-80	notch receptor 1	Homo sapiens	4-10
31578228-6	2019	RESULTS: In vitro ibrutinib treatment of CLL significantly reduced activated NOTCH1/2 and induced dephosphorylation of eIF4E, a NOTCH target in CLL.	ibrutinib	18-27	notch receptor 1	Homo sapiens	77-85
31578228-12	2019	The ibrutinib clinical efficacy was associated with NOTCH1 activity downregulation that deepened over time.	ibrutinib	4-13	notch receptor 1	Homo sapiens	52-58
31578228-6	2019	RESULTS: In vitro ibrutinib treatment of CLL significantly reduced activated NOTCH1/2 and induced dephosphorylation of eIF4E, a NOTCH target in CLL.	ibrutinib	18-27	eukaryotic translation initiation factor 4E	Homo sapiens	119-124
31921116-7	2019	The influence of ibrutinib on antigen-specific CD8+ T cell function was assessed by HLA-peptide tetramers and revealed increased IFNgamma and TNFalpha cytokine responses following stimulation with CMV or EBV peptides together with a 55% reduction in the frequency of "inflated" virus-specific CD8+ T cells.	ibrutinib	17-26	interferon gamma	Homo sapiens	129-137
31364190-1	2019	RATIONALE: Ibrutinib is a potent Bruton"s tyrosine kinase (BTK) inhibitor, which has been shown promising efficacy against various B-cell malignancies.	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	33-57
31364190-1	2019	RATIONALE: Ibrutinib is a potent Bruton"s tyrosine kinase (BTK) inhibitor, which has been shown promising efficacy against various B-cell malignancies.	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	59-62
31921116-7	2019	The influence of ibrutinib on antigen-specific CD8+ T cell function was assessed by HLA-peptide tetramers and revealed increased IFNgamma and TNFalpha cytokine responses following stimulation with CMV or EBV peptides together with a 55% reduction in the frequency of "inflated" virus-specific CD8+ T cells.	ibrutinib	17-26	tumor necrosis factor	Homo sapiens	142-150
31817171-9	2019	We herein provide evidence that JAK2/STAT3 signaling might play a key role in the regulation of CLL-BMSC interactions and its inhibition enhances ibrutinib, counteracting the bone marrow niche.	ibrutinib	146-155	Janus kinase 2	Homo sapiens	32-36
31809536-3	2019	We explored the potential to prevent FcgammaRIIA-induced platelet activation by BTK inhibitors (BTKi"s) approved (ibrutinib, acalabrutinib) or in clinical trials (zanubrutinib [BGB-3111] and tirabrutinib [ONO/GS-4059]) for B-cell malignancies, or in trials for autoimmune diseases (evobrutinib, fenebrutinib [GDC-0853]).	ibrutinib	114-123	Fc gamma receptor IIa	Homo sapiens	37-48
31809536-3	2019	We explored the potential to prevent FcgammaRIIA-induced platelet activation by BTK inhibitors (BTKi"s) approved (ibrutinib, acalabrutinib) or in clinical trials (zanubrutinib [BGB-3111] and tirabrutinib [ONO/GS-4059]) for B-cell malignancies, or in trials for autoimmune diseases (evobrutinib, fenebrutinib [GDC-0853]).	ibrutinib	114-123	inhibitor of Bruton tyrosine kinase	Homo sapiens	96-100
31809536-5	2019	The concentrations that inhibit 50% (IC50) of FcgammaRIIA cross-linking-induced platelet aggregation were for the irreversible BTKi"s ibrutinib 0.08 microM, zanubrutinib 0.11 microM, acalabrutinib 0.38 microM, tirabrutinib 0.42 microM, evobrutinib 1.13 microM, and for the reversible BTKi fenebrutinib 0.011 microM.	ibrutinib	134-143	Fc gamma receptor IIa	Homo sapiens	46-57
31809536-5	2019	The concentrations that inhibit 50% (IC50) of FcgammaRIIA cross-linking-induced platelet aggregation were for the irreversible BTKi"s ibrutinib 0.08 microM, zanubrutinib 0.11 microM, acalabrutinib 0.38 microM, tirabrutinib 0.42 microM, evobrutinib 1.13 microM, and for the reversible BTKi fenebrutinib 0.011 microM.	ibrutinib	134-143	inhibitor of Bruton tyrosine kinase	Homo sapiens	127-131
31809536-9	2019	A single oral intake of ibrutinib (280 mg) was sufficient for a rapid and sustained suppression of platelet FcgammaRIIA activation.	ibrutinib	24-33	Fc gamma receptor IIa	Homo sapiens	108-119
31817171-9	2019	We herein provide evidence that JAK2/STAT3 signaling might play a key role in the regulation of CLL-BMSC interactions and its inhibition enhances ibrutinib, counteracting the bone marrow niche.	ibrutinib	146-155	signal transducer and activator of transcription 3	Homo sapiens	37-42
31355927-6	2019	Two cell lines presented a discordant response to first and second generation BTK inhibitors, probably due to the inhibition by ibrutinib of kinases other than BTK.	ibrutinib	128-137	Bruton tyrosine kinase	Homo sapiens	78-81
31801949-0	2019	Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K/AKT activation in B-cell lymphoid malignancies.	ibrutinib	32-41	Bruton tyrosine kinase	Homo sapiens	14-17
31801949-0	2019	Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K/AKT activation in B-cell lymphoid malignancies.	ibrutinib	32-41	forkhead box O3	Homo sapiens	72-78
31801949-0	2019	Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K/AKT activation in B-cell lymphoid malignancies.	ibrutinib	32-41	AKT serine/threonine kinase 1	Homo sapiens	103-106
31801949-2	2019	Ibrutinib, an FDA approved, orally administered BTK inhibitor, has demonstrated high response rates, however, complete responses are infrequent and acquired resistance to BTK inhibition can emerge.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	48-51
31801949-2	2019	Ibrutinib, an FDA approved, orally administered BTK inhibitor, has demonstrated high response rates, however, complete responses are infrequent and acquired resistance to BTK inhibition can emerge.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	171-174
31801949-5	2019	Inhibition of PI3K and AKT using idelalisib and MK2206, respectively increased ibrutinib-induced apoptosis in IB-R cells by downregulation of pAKT473 and restoring FOXO3a levels, demonstrating the importance of these cell survival factors for ibrutinib-resistance.	ibrutinib	79-88	AKT serine/threonine kinase 1	Homo sapiens	23-26
31801949-5	2019	Inhibition of PI3K and AKT using idelalisib and MK2206, respectively increased ibrutinib-induced apoptosis in IB-R cells by downregulation of pAKT473 and restoring FOXO3a levels, demonstrating the importance of these cell survival factors for ibrutinib-resistance.	ibrutinib	79-88	forkhead box O3	Homo sapiens	164-170
31801949-5	2019	Inhibition of PI3K and AKT using idelalisib and MK2206, respectively increased ibrutinib-induced apoptosis in IB-R cells by downregulation of pAKT473 and restoring FOXO3a levels, demonstrating the importance of these cell survival factors for ibrutinib-resistance.	ibrutinib	243-252	AKT serine/threonine kinase 1	Homo sapiens	23-26
31801949-6	2019	Notably, the exportin 1 inhibitor, selinexor synergized with ibrutinib in IB-R cells and restored nuclear abundance of FOXO3a and PTEN, suggesting that nuclear accumulation of FOXO3a and PTEN facilitates increase in ibrutinib-induced apoptosis in IB-R cells.	ibrutinib	61-70	exportin 1	Homo sapiens	13-23
31801949-7	2019	These data demonstrate that reactivation of FOXO3a nuclear function enhances the efficacy of ibrutinib and overcomes acquired resistance to ibrutinib.	ibrutinib	93-102	forkhead box O3	Homo sapiens	44-50
31801949-7	2019	These data demonstrate that reactivation of FOXO3a nuclear function enhances the efficacy of ibrutinib and overcomes acquired resistance to ibrutinib.	ibrutinib	140-149	forkhead box O3	Homo sapiens	44-50
31801949-8	2019	Together, these findings reveal a novel mechanism that confers ibrutinib resistance via aberrant nuclear/cytoplasmic subcellular localization of FOXO3a and could be exploited by rational therapeutic combination regimens for effectively treating lymphoid malignancies.	ibrutinib	63-72	forkhead box O3	Homo sapiens	145-151
31364164-3	2019	However, the mutant BtkC481S poses a major challenge in the management of B-cell malignancies by disrupting the formation of the covalent bond between BTK and irreversible inhibitors, such as ibrutinib.	ibrutinib	192-201	Bruton tyrosine kinase	Homo sapiens	151-154
31364164-4	2019	The present studies were designed to develop novel BTK inhibitors targeting ibrutinib-resistant BtkC481S mutation.	ibrutinib	76-85	Bruton tyrosine kinase	Homo sapiens	51-54
31364164-12	2019	These findings establish XMU-MP-3 as a novel inhibitor of BTK, which could serve as both a tool compound and a lead for further drug development in BTK relevant B-cell malignancies, especially those with the acquired ibrutinib-resistant C481S mutation.	ibrutinib	217-226	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	58-61
31638169-0	2019	Ibrutinib in CLL/SLL: From bench to bedside (Review).	ibrutinib	0-9	solute carrier family 35 member B2	Homo sapiens	13-20
31639635-5	2019	We observed a dramatic reduction of neutrophils oxidative burst, Fc gamma receptors (FcgammaRs)-mediated degranulation and IL-8 plasma levels already after the first forty-eight hours of therapy with ibrutinib.	ibrutinib	200-209	C-X-C motif chemokine ligand 8	Homo sapiens	123-127
31639635-9	2019	In conclusion, during the initial phases of ibrutinib therapy, the reduction of IL-8, NE, myeloperoxidase (MPO) levels and oxidative burst negatively impacted on mechanisms involved in neutrophils microbicidal activity.	ibrutinib	44-53	C-X-C motif chemokine ligand 8	Homo sapiens	80-84
31639635-9	2019	In conclusion, during the initial phases of ibrutinib therapy, the reduction of IL-8, NE, myeloperoxidase (MPO) levels and oxidative burst negatively impacted on mechanisms involved in neutrophils microbicidal activity.	ibrutinib	44-53	myeloperoxidase	Homo sapiens	90-105
31639635-9	2019	In conclusion, during the initial phases of ibrutinib therapy, the reduction of IL-8, NE, myeloperoxidase (MPO) levels and oxidative burst negatively impacted on mechanisms involved in neutrophils microbicidal activity.	ibrutinib	44-53	myeloperoxidase	Homo sapiens	107-110
31638169-3	2019	Ibrutinib, a BTK inhibitor, has demonstrated marked efficacy and tolerability in treatment-naive, relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-16
31638169-3	2019	Ibrutinib, a BTK inhibitor, has demonstrated marked efficacy and tolerability in treatment-naive, relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL).	ibrutinib	0-9	solute carrier family 35 member B2	Homo sapiens	179-182
31638169-4	2019	Ibrutinib has been approved by the Food and Drug Administration (FDA) for the treatment of CLL/SLL, MCL, marginal zone lymphoma and Waldenstrom macroglobulinemia and by the China FDA for the treatment of CLL/SLL and MCL.	ibrutinib	0-9	solute carrier family 35 member B2	Homo sapiens	95-98
31638169-4	2019	Ibrutinib has been approved by the Food and Drug Administration (FDA) for the treatment of CLL/SLL, MCL, marginal zone lymphoma and Waldenstrom macroglobulinemia and by the China FDA for the treatment of CLL/SLL and MCL.	ibrutinib	0-9	solute carrier family 35 member B2	Homo sapiens	208-211
31638169-6	2019	The aim of the present review was mainly to cover the clinical developments regarding the use of ibrutinib in the treatment of CLL/SLL, as well as its safety and toxicity profile.	ibrutinib	97-106	solute carrier family 35 member B2	Homo sapiens	131-134
31286638-1	2019	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is effective in the treatment of human chronic lymphocytic leukaemia and mantle cell lymphoma.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
31286638-1	2019	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib is effective in the treatment of human chronic lymphocytic leukaemia and mantle cell lymphoma.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
31286638-5	2019	Using flow cytometry, we found that ibrutinib suppresses phosphorylation of BTK and of downstream STAT5 in both MC lines.	ibrutinib	36-45	Bruton tyrosine kinase	Canis lupus familiaris	76-79
31286638-6	2019	In addition, ibrutinib decreased proliferation of neoplastic MCs, with IC50 values ranging between 0.1 and 1 muM in primary MCT cells and between 1 and 3 muM in C2 and NI-1 cells.	ibrutinib	13-22	complement C2	Canis lupus familiaris	161-172
31762943-0	2019	Correction: The combination effect of homoharringtonine and ibrutinib on FLT3-ITD mutant acute myeloid leukemia.	ibrutinib	60-69	fms related receptor tyrosine kinase 3	Homo sapiens	73-77
31766355-1	2019	Ibrutinib is the first Bruton"s tyrosine kinase (BTK) inhibitor, which showed significant clinical activity in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) patients regardless of cytogenetic risk factors.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	23-47
31766355-1	2019	Ibrutinib is the first Bruton"s tyrosine kinase (BTK) inhibitor, which showed significant clinical activity in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) patients regardless of cytogenetic risk factors.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	49-52
31622099-4	2019	Further optimization led to 6-cyanomethyl-5-azaquinazoline 13, a selective IRAK4 inhibitor, which proved efficacious in combination with ibrutinib, while showing very little activity as a single agent up to 100 mg/kg.	ibrutinib	137-146	interleukin 1 receptor associated kinase 4	Homo sapiens	75-80
31740673-5	2019	The results of this computational framework highlight a prominent role of the immune system in metabolic syndrome and suggest a potential use of the BTK inhibitor ibrutinib as a novel pharmacological treatment.	ibrutinib	163-172	Bruton agammaglobulinemia tyrosine kinase	Danio rerio	149-152
31445021-0	2019	Inhibition of human UDP-glucuronosyltransferase (UGT) enzymes by kinase inhibitors: Effects of dabrafenib, ibrutinib, nintedanib, trametinib and BIBF 1202.	ibrutinib	107-116	UDP glucuronosyltransferase family 1 member A complex locus	Homo sapiens	49-52
31445021-2	2019	The present study characterised the effects of four additional drugs in this class, dabrafenib, ibrutinib, nintedanib and trametinib, on human UGT enzyme activities in vitro.	ibrutinib	96-105	UDP glucuronosyltransferase family 1 member A complex locus	Homo sapiens	143-146
31445021-3	2019	Dabrafenib, ibrutinib, nintedanib and trametinib were potent inhibitors of human liver microsomal UGT1A1; Ki,u values ranged from 1.1 to 7.5 microM.	ibrutinib	12-21	UDP glucuronosyltransferase family 1 member A1	Homo sapiens	98-104
31365830-5	2019	The inhibition of BTK by ibrutinib noticeably diminish the CaP-induced up-regulation of IL-6 and p-ERK in mice.	ibrutinib	25-34	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	18-21
31267520-0	2019	CXCR4 mutation subtypes impact response and survival outcomes in patients with Waldenstrom macroglobulinaemia treated with ibrutinib.	ibrutinib	123-132	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
31267520-2	2019	CXCR4 mutations are detected in 30-40% of patients with WM and associate with lower rates of response and shorter PFS to ibrutinib therapy.	ibrutinib	121-130	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
31267520-9	2019	Our results suggest different response and PFS rates to ibrutinib for WM patients with CXCR4NS and CXCR4FS , and advocate in favour of CXCR4 mutational testing as well as CXCR4-directed therapy.	ibrutinib	56-65	C-X-C motif chemokine receptor 4	Homo sapiens	99-106
31267520-9	2019	Our results suggest different response and PFS rates to ibrutinib for WM patients with CXCR4NS and CXCR4FS , and advocate in favour of CXCR4 mutational testing as well as CXCR4-directed therapy.	ibrutinib	56-65	C-X-C motif chemokine receptor 4	Homo sapiens	87-92
31267520-9	2019	Our results suggest different response and PFS rates to ibrutinib for WM patients with CXCR4NS and CXCR4FS , and advocate in favour of CXCR4 mutational testing as well as CXCR4-directed therapy.	ibrutinib	56-65	C-X-C motif chemokine receptor 4	Homo sapiens	99-104
31764119-7	2019	Second-generation BTKis are under development, which differ from ibrutinib, the first-in-class BTKi, in their specificity for BTK, and therefore may differentiate themselves from ibrutinib in terms of adverse effects or efficacy.	ibrutinib	65-74	inhibitor of Bruton tyrosine kinase	Homo sapiens	18-22
31764119-7	2019	Second-generation BTKis are under development, which differ from ibrutinib, the first-in-class BTKi, in their specificity for BTK, and therefore may differentiate themselves from ibrutinib in terms of adverse effects or efficacy.	ibrutinib	65-74	Bruton tyrosine kinase	Homo sapiens	18-21
31430829-5	2019	The novel Bruton Tyrosine Kinase inhibitor ibrutinib has shown CNS-penetrating properties, and recent data suggest a therapeutic role in BNS.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	10-32
31764118-4	2019	Elucidation of these signaling pathways has defined physiologic targets for drugs, such as ibrutinib, which inhibit Bruton tyrosine kinase and are therapeutically effective.	ibrutinib	91-100	Bruton tyrosine kinase	Homo sapiens	116-138
31365830-5	2019	The inhibition of BTK by ibrutinib noticeably diminish the CaP-induced up-regulation of IL-6 and p-ERK in mice.	ibrutinib	25-34	interleukin 6	Mus musculus	88-92
31365830-5	2019	The inhibition of BTK by ibrutinib noticeably diminish the CaP-induced up-regulation of IL-6 and p-ERK in mice.	ibrutinib	25-34	mitogen-activated protein kinase 1	Mus musculus	99-102
31365830-7	2019	The expressions of p-BTK and p-ERK in DRG primary cells reached maximum levels at 1 and 10 min, respectively, after treatment of recombinant IL-6 and were significantly reduced by treatment of IL-6 along with ibrutinib.	ibrutinib	209-218	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	21-24
31365830-7	2019	The expressions of p-BTK and p-ERK in DRG primary cells reached maximum levels at 1 and 10 min, respectively, after treatment of recombinant IL-6 and were significantly reduced by treatment of IL-6 along with ibrutinib.	ibrutinib	209-218	eukaryotic translation initiation factor 2 alpha kinase 3	Mus musculus	29-34
31365830-7	2019	The expressions of p-BTK and p-ERK in DRG primary cells reached maximum levels at 1 and 10 min, respectively, after treatment of recombinant IL-6 and were significantly reduced by treatment of IL-6 along with ibrutinib.	ibrutinib	209-218	interleukin 6	Mus musculus	141-145
31365830-7	2019	The expressions of p-BTK and p-ERK in DRG primary cells reached maximum levels at 1 and 10 min, respectively, after treatment of recombinant IL-6 and were significantly reduced by treatment of IL-6 along with ibrutinib.	ibrutinib	209-218	interleukin 6	Mus musculus	193-197
31473630-7	2019	Mutated SF3B1 is present in 9%-15% of chronic lymphocytic leukaemia cases and on its own correlates with improved responsiveness to ibrutinib, but is associated with additional adverse genetic abnormalities including TP53 and ATM mutations, which traditionally confer adverse outcomes.	ibrutinib	132-141	splicing factor 3b subunit 1	Homo sapiens	8-13
31606655-2	2019	We report screening data from the iMYC trial, an ongoing phase II study assessing ibrutinib monotherapy in advanced pretreated MYC- and/or HER2-amplified oesophagogastric cancer, representing the first attempt to prospectively identify MYC amplifications in this tumour type for the purposes of therapeutic targeting.	ibrutinib	82-91	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	127-130
31591468-6	2019	The approval of the oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib alone and in combination with rituximab has expanded the treatment options for WM patients.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	25-47
31591468-6	2019	The approval of the oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib alone and in combination with rituximab has expanded the treatment options for WM patients.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	49-52
31644524-0	2019	Effect and Mechanism of the Bruton Tyrosine Kinase (Btk) Inhibitor Ibrutinib on Rat Model of Diabetic Foot Ulcers.	ibrutinib	67-76	Bruton tyrosine kinase	Rattus norvegicus	28-50
31644524-0	2019	Effect and Mechanism of the Bruton Tyrosine Kinase (Btk) Inhibitor Ibrutinib on Rat Model of Diabetic Foot Ulcers.	ibrutinib	67-76	Bruton tyrosine kinase	Rattus norvegicus	52-55
31644524-2	2019	Ibrutinib is a Bruton tyrosine kinase (Btk) inhibitor, and the role and mechanism of ibrutinib on the diabetic foot have not been elucidated.	ibrutinib	0-9	Bruton tyrosine kinase	Rattus norvegicus	15-37
31644524-2	2019	Ibrutinib is a Bruton tyrosine kinase (Btk) inhibitor, and the role and mechanism of ibrutinib on the diabetic foot have not been elucidated.	ibrutinib	0-9	Bruton tyrosine kinase	Rattus norvegicus	39-42
31310800-1	2019	Ibrutinib, an inhibitor of Bruton tyrosine kinase (BTK), has shown promising pharmacologic effects in acute myeloid leukemia (AML).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	27-49
31511358-10	2019	In contrast to tirabrutinib, ibrutinib had inhibitory effects on T cell activation, probably because of ITK inhibition.	ibrutinib	29-38	IL2 inducible T cell kinase	Homo sapiens	104-107
31570491-0	2019	CXCR4 S338X clonality is an important determinant of ibrutinib outcomes in patients with Waldenstrom macroglobulinemia.	ibrutinib	53-62	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
31310800-1	2019	Ibrutinib, an inhibitor of Bruton tyrosine kinase (BTK), has shown promising pharmacologic effects in acute myeloid leukemia (AML).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	51-54
30819907-9	2019	p66Shc expression declined with disease progression in Emu-TCL1 mice and could be restored by treatment with the Bruton tyrosine kinase inhibitor ibrutinib.	ibrutinib	146-155	src homology 2 domain-containing transforming protein C1	Mus musculus	0-6
31343930-7	2019	Very good partial response (VGPR) and progression-free survival (PFS) rates to ibrutinib, with and without rituximab, appeared lower in CXCR4MUT than in CXCR4WT patients.	ibrutinib	79-88	C-X-C motif chemokine receptor 4	Homo sapiens	136-141
30819907-9	2019	p66Shc expression declined with disease progression in Emu-TCL1 mice and could be restored by treatment with the Bruton tyrosine kinase inhibitor ibrutinib.	ibrutinib	146-155	T cell lymphoma breakpoint 1	Mus musculus	59-63
30819907-9	2019	p66Shc expression declined with disease progression in Emu-TCL1 mice and could be restored by treatment with the Bruton tyrosine kinase inhibitor ibrutinib.	ibrutinib	146-155	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	113-135
30821551-6	2019	Induction of PD-L1 was attenuated by concurrent treatment with ibrutinib or duvelisib, suggesting BTK and PI3K are important mediators of PD-L1 expression.	ibrutinib	63-72	CD274 molecule	Sus scrofa	13-18
31420873-1	2019	Ibrutinib, a first-generation Bruton"s tyrosine kinase (BTK) inhibitor, could improve immunity of relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	30-54
31420873-1	2019	Ibrutinib, a first-generation Bruton"s tyrosine kinase (BTK) inhibitor, could improve immunity of relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	56-59
31197205-11	2019	PD-L1 was down-regulated by ibrutinib in a xenograft mouse model and correlated with slower tumor growth.	ibrutinib	28-37	CD274 antigen	Mus musculus	0-5
30940906-8	2019	Further analyses of serial samples from ibrutinib-treated patients (n = 8) highlighted a rapid decrease of CSF1, IL-10, and CD163 in responsive patients.	ibrutinib	40-49	colony stimulating factor 1	Homo sapiens	107-111
30940906-8	2019	Further analyses of serial samples from ibrutinib-treated patients (n = 8) highlighted a rapid decrease of CSF1, IL-10, and CD163 in responsive patients.	ibrutinib	40-49	interleukin 10	Homo sapiens	113-118
30940906-8	2019	Further analyses of serial samples from ibrutinib-treated patients (n = 8) highlighted a rapid decrease of CSF1, IL-10, and CD163 in responsive patients.	ibrutinib	40-49	CD163 molecule	Homo sapiens	124-129
30821551-6	2019	Induction of PD-L1 was attenuated by concurrent treatment with ibrutinib or duvelisib, suggesting BTK and PI3K are important mediators of PD-L1 expression.	ibrutinib	63-72	Bruton tyrosine kinase	Homo sapiens	98-101
30821551-6	2019	Induction of PD-L1 was attenuated by concurrent treatment with ibrutinib or duvelisib, suggesting BTK and PI3K are important mediators of PD-L1 expression.	ibrutinib	63-72	CD274 molecule	Sus scrofa	138-143
31505252-4	2019	Ibrutinib is primarily a BTK inhibitor, however it is reported to be an ITK inhibitor as well.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	25-28
31505252-4	2019	Ibrutinib is primarily a BTK inhibitor, however it is reported to be an ITK inhibitor as well.	ibrutinib	0-9	IL2 inducible T cell kinase	Mus musculus	72-75
31505252-7	2019	However, at a much higher dose, i.e. 250 mug/mouse, Ibrutinib remarkably suppressed both Th17/Th2 and lymphocytic/neutrophilic/eosinophilic airway inflammation.	ibrutinib	52-61	heart and neural crest derivatives expressed 2	Mus musculus	94-97
31505252-8	2019	At molecular level, Ibrutinib suppressed phosphorylation of BTK in neutrophils at lower doses and ITK in CD4 + T cells at higher doses in CE-treated mice.	ibrutinib	20-29	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	60-63
31505252-5	2019	In this study, we sought to determine the effect of Ibrutinib on Th1, Th17 and Th2 immune responses in a cockroach allergen extract (CE)-induced mixed granulocytic (eosinophilic and neutrophilic) mouse model in preventative mode.	ibrutinib	52-61	negative elongation factor complex member C/D, Th1l	Mus musculus	65-68
31505252-5	2019	In this study, we sought to determine the effect of Ibrutinib on Th1, Th17 and Th2 immune responses in a cockroach allergen extract (CE)-induced mixed granulocytic (eosinophilic and neutrophilic) mouse model in preventative mode.	ibrutinib	52-61	heart and neural crest derivatives expressed 2	Mus musculus	79-82
31505252-8	2019	At molecular level, Ibrutinib suppressed phosphorylation of BTK in neutrophils at lower doses and ITK in CD4 + T cells at higher doses in CE-treated mice.	ibrutinib	20-29	CD4 antigen	Mus musculus	105-108
31505252-10	2019	Ibrutinib was able to control granulocytic inflammation along with Th2/Th17 immune response in therapeutic mode whereas dexamethasone limited only Th2/eosinophilic inflammation.	ibrutinib	0-9	heart and neural crest derivatives expressed 2	Mus musculus	67-70
31428514-5	2019	Targeted therapies with small molecule inhibitors against Bruton tyrosine kinase (BTK) such as ibrutinib and acalabrutinib are playing a major role for treatment of patients with either treatment-naive or refractory/relapsed CLL.	ibrutinib	95-104	Bruton tyrosine kinase	Homo sapiens	58-80
31505252-11	2019	Thus, Ibrutinib has the potential to suppress both Th17/Th2 and neutrophilic/eosinophilic inflammation during mixed granulocytic asthma and therefore may be pursued as alternative therapeutic option in difficult-to-treat asthma which is resistant to corticosteroids.	ibrutinib	6-15	heart and neural crest derivatives expressed 2	Mus musculus	56-59
31368705-1	2019	Bruton"s tyrosine kinase (BTK) inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies.	ibrutinib	50-59	Bruton tyrosine kinase	Homo sapiens	0-24
31368705-1	2019	Bruton"s tyrosine kinase (BTK) inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies.	ibrutinib	50-59	Bruton tyrosine kinase	Homo sapiens	26-29
31552054-15	2019	Delayed administration of ibrutinib and acalabrutinib attenuated the decline of EF, FS, and FAC caused by CLP and also reduced the activation of BTK, NF-kappaB, and NLRP3 inflammasome.	ibrutinib	26-35	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	145-148
31552054-15	2019	Delayed administration of ibrutinib and acalabrutinib attenuated the decline of EF, FS, and FAC caused by CLP and also reduced the activation of BTK, NF-kappaB, and NLRP3 inflammasome.	ibrutinib	26-35	NLR family, pyrin domain containing 3	Mus musculus	165-170
31552054-17	2019	Our study revealed that delayed intravenous administration of ibrutinib or acalabrutinib attenuated the cardiac dysfunction associated with sepsis by inhibiting BTK, reducing NF-kappaB activation and the activation of the inflammasome.	ibrutinib	62-71	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	161-164
31552054-20	2019	Thus, the FDA-approved BTK inhibitors ibrutinib and acalabrutinib may be repurposed for the use in sepsis.	ibrutinib	38-47	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	23-26
30760164-3	2019	Of interest, ibrutinib, a Bruton tyrosine kinase inhibitor has also displayed efficacy in Bing-Neel syndrome.	ibrutinib	13-22	Bruton tyrosine kinase	Homo sapiens	26-48
31528323-0	2019	Response to Ibrutinib of a Refractory IgA Lymphoplasmacytic Lymphoma Carrying the MYD88 L265P Gene Mutation.	ibrutinib	12-21	MYD88 innate immune signal transduction adaptor	Homo sapiens	82-87
31528323-8	2019	Given the identification of MYD88 L265P mutation, in February 2018 our patient started ibrutinib off-label.	ibrutinib	87-96	MYD88 innate immune signal transduction adaptor	Homo sapiens	28-33
31648477-0	2019	[Ibrutinib combined with CAR-T cells in the treatment of del (17p) chronic lymphocytic leukemia with BCL-2 inhibitor resistance: a case report and literature review].	ibrutinib	1-10	BCL2 apoptosis regulator	Homo sapiens	101-106
31648477-1	2019	Objective: To improve the knowledge and experience of ibrutinib combined with CAR-T cells in the treatment of high-risk chronic lymphoblastic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) with TP53 gene aberration.	ibrutinib	54-63	tumor protein p53	Homo sapiens	207-211
31648477-2	2019	Methods: One case of del (17p) CLL patients with BCL-2 inhibitor resistance was treated with ibrutinib combined with CAR-T cells, successfully bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and the relative literatures were reviewed.	ibrutinib	93-102	BCL2 apoptosis regulator	Homo sapiens	49-54
31648477-8	2019	The spleen was enlarged to 16 cm below the ribs, the neck lymph nodes was rapidly enlarged, and the superior vena cava syndrome appeared, which were mainly attributed to venetoclax resistance; so BTK inhibitor (ibrutinib) was used continuously after venetoclax discontinuation.	ibrutinib	211-220	Bruton tyrosine kinase	Homo sapiens	196-199
31646085-7	2019	Ibrutinib, an irreversible inhibitor of Bruton"s tyrosine kinase (BTK), is in clinical use for the treatment of B- cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	40-64
31646085-7	2019	Ibrutinib, an irreversible inhibitor of Bruton"s tyrosine kinase (BTK), is in clinical use for the treatment of B- cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	66-69
31646085-9	2019	Furthermore, ibrutinib is able to inhibit BTK phosphorylation in TAM generated in vitro.	ibrutinib	13-22	Bruton tyrosine kinase	Homo sapiens	42-45
31646085-10	2019	Treatment of TAM with ibrutinib significantly impaired the ability of these cells to produce IL-1beta.	ibrutinib	22-31	interleukin 1 beta	Homo sapiens	93-101
31646085-11	2019	The present study provides evidence that BTK physically associates with the NLRP3 inflammasome and that inhibition of BTK with ibrutinib can impair the production of IL-1beta by in vitro generated TAM.	ibrutinib	127-136	Bruton tyrosine kinase	Homo sapiens	118-121
31646085-11	2019	The present study provides evidence that BTK physically associates with the NLRP3 inflammasome and that inhibition of BTK with ibrutinib can impair the production of IL-1beta by in vitro generated TAM.	ibrutinib	127-136	interleukin 1 beta	Homo sapiens	166-174
31508518-5	2019	Ibrutinib treatment resulted in suppression of BTK and other downstream targets including PI3K, mTOR and RICTOR.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	47-50
31508518-5	2019	Ibrutinib treatment resulted in suppression of BTK and other downstream targets including PI3K, mTOR and RICTOR.	ibrutinib	0-9	mechanistic target of rapamycin kinase	Mus musculus	96-100
31508518-5	2019	Ibrutinib treatment resulted in suppression of BTK and other downstream targets including PI3K, mTOR and RICTOR.	ibrutinib	0-9	RPTOR independent companion of MTOR, complex 2	Mus musculus	105-111
31555576-7	2019	The continuous administration of ibrutinib single agent has led to prolonged PFS and OS in relapsed/refractory and treatment naive CLL, including those with TP53 deletion/mutation or unmutated IGHV genes, though the clinical responses are rarely complete.	ibrutinib	33-42	tumor protein p53	Homo sapiens	157-161
31555576-7	2019	The continuous administration of ibrutinib single agent has led to prolonged PFS and OS in relapsed/refractory and treatment naive CLL, including those with TP53 deletion/mutation or unmutated IGHV genes, though the clinical responses are rarely complete.	ibrutinib	33-42	immunoglobulin heavy variable 3-69-1 (pseudogene)	Homo sapiens	193-197
31695539-3	2019	Interestingly, clinical responses to ibrutinib have been shown to be dependent on patients" MYD88 and CXCR4 mutational status.	ibrutinib	37-46	MYD88 innate immune signal transduction adaptor	Homo sapiens	92-97
31695539-3	2019	Interestingly, clinical responses to ibrutinib have been shown to be dependent on patients" MYD88 and CXCR4 mutational status.	ibrutinib	37-46	C-X-C motif chemokine receptor 4	Homo sapiens	102-107
31292113-3	2019	Whereas TTFT risk stratification remains similar over time, TTP and OS have changed dramatically with the introduction of targeted therapies, such as the Bruton tyrosine kinase inhibitor ibrutinib.	ibrutinib	187-196	Bruton tyrosine kinase	Homo sapiens	154-176
31428514-5	2019	Targeted therapies with small molecule inhibitors against Bruton tyrosine kinase (BTK) such as ibrutinib and acalabrutinib are playing a major role for treatment of patients with either treatment-naive or refractory/relapsed CLL.	ibrutinib	95-104	Bruton tyrosine kinase	Homo sapiens	82-85
31382969-4	2019	This expression was dependent on activation of either NF-kappaB, JAK1/JAK2 or BTK pathways since these pathways were activated in tumor B-cells and ex vivo treatment with the inhibitory molecules PHA-408, ruxolitinib and ibrutinib led to decrease of its expression.	ibrutinib	221-230	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	54-63
31406628-1	2019	Background: The Bruton"s Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models.	ibrutinib	57-66	Bruton tyrosine kinase	Homo sapiens	16-40
31406628-1	2019	Background: The Bruton"s Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models.	ibrutinib	57-66	Bruton tyrosine kinase	Homo sapiens	42-45
31406628-1	2019	Background: The Bruton"s Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models.	ibrutinib	57-66	keratin 20	Homo sapiens	147-151
31243043-0	2019	Prevalence of BTK and PLCG2 mutations in a real-life CLL cohort still on ibrutinib after 3 years: a FILO group study.	ibrutinib	73-82	Bruton tyrosine kinase	Homo sapiens	14-17
31243043-0	2019	Prevalence of BTK and PLCG2 mutations in a real-life CLL cohort still on ibrutinib after 3 years: a FILO group study.	ibrutinib	73-82	phospholipase C gamma 2	Homo sapiens	22-27
31243043-1	2019	Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (BTK) and/or phospholipase Cgamma2 (PLCG2) genes.	ibrutinib	140-149	Bruton tyrosine kinase	Homo sapiens	176-198
31243043-1	2019	Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (BTK) and/or phospholipase Cgamma2 (PLCG2) genes.	ibrutinib	140-149	Bruton tyrosine kinase	Homo sapiens	200-203
31243043-1	2019	Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (BTK) and/or phospholipase Cgamma2 (PLCG2) genes.	ibrutinib	140-149	phospholipase C gamma 2	Homo sapiens	235-240
31406628-2	2019	We investigated how antibody-dependent cellular cytotoxicity (ADCC) induced by type I/II anti-CD20 antibodies was affected by treatment with ibrutinib in MCL.	ibrutinib	141-150	keratin 20	Homo sapiens	94-98
31229160-6	2019	Differential responses are also seen with novel agents such as the BTK inhibitor ibrutinib.	ibrutinib	81-90	Bruton tyrosine kinase	Homo sapiens	67-70
31406628-7	2019	Conclusion: Ibrutinib negatively affects anti-CD20 induced cell death in MCL, not reversed by lenalidomide.	ibrutinib	12-21	keratin 20	Homo sapiens	46-50
31184501-1	2019	The Bruton"s tyrosine kinase inhibitor ibrutinib represents a highly effective single substance in the treatment of Waldenstrom"s macroglobulinemia.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	4-28
31363127-4	2019	Conversely, an inhibitor of BTK used clinically (ibrutinib) induces bioenergetic stress responses that in turn affect ibrutinib resistance.	ibrutinib	49-58	Bruton tyrosine kinase	Homo sapiens	28-31
31365801-8	2019	In a subgroup analysis involving patients without immunoglobulin heavy-chain variable region (IGHV) mutation, ibrutinib-rituximab resulted in better progression-free survival than chemoimmunotherapy (90.7% vs. 62.5% at 3 years; hazard ratio for progression or death, 0.26; 95% CI, 0.14 to 0.50).	ibrutinib	110-119	immunoglobulin heavy variable 3/OR16-17 (non-functional)	Homo sapiens	94-98
31365801-9	2019	The 3-year progression-free survival among patients with IGHV mutation was 87.7% in the ibrutinib-rituximab group and 88.0% in the chemoimmunotherapy group (hazard ratio for progression or death, 0.44; 95% CI, 0.14 to 1.36).	ibrutinib	88-97	immunoglobulin heavy variable 3/OR16-17 (non-functional)	Homo sapiens	57-61
31363127-4	2019	Conversely, an inhibitor of BTK used clinically (ibrutinib) induces bioenergetic stress responses that in turn affect ibrutinib resistance.	ibrutinib	118-127	Bruton tyrosine kinase	Homo sapiens	28-31
31363127-5	2019	Although the detailed molecular mechanisms are still to be defined, our work shows for the first time that in primary B cells, metabolic stressors enhance BTK signaling and suggest that metabolic rewiring to hyperglycemia affects ibrutinib resistance in TP53 deficient chronic lymphocytic leukemia (CLL) lymphocytes.	ibrutinib	230-239	tumor protein p53	Homo sapiens	254-258
31372077-1	2019	Background: Ibrutinib is a Bruton"s tyrosine-kinase (BTK) inhibitor that is approved as a second-line treatment in chronic lymphocytic leukemia (CLL).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	27-51
31087308-2	2019	Patients with X-linked agammaglobulinemia due to hereditary Btk deficiency do not show bleeding, but a mild bleeding tendency is observed in high dose therapy of B-cell malignancies with ibrutinib and novel second-generation irreversible Btk inhibitors (acalabrutinib and ONO/GS-4059).	ibrutinib	187-196	Bruton tyrosine kinase	Homo sapiens	60-63
31372077-1	2019	Background: Ibrutinib is a Bruton"s tyrosine-kinase (BTK) inhibitor that is approved as a second-line treatment in chronic lymphocytic leukemia (CLL).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	53-56
31372077-6	2019	We also identify del13q14.3 as an adverse predictor of response to ibrutinib with respect to both overall survival (p=0.014) and PFS (p=0.008), suggesting that these patients may be better suited to receiving the BCL2 inhibitor venetoclax.	ibrutinib	67-76	BCL2 apoptosis regulator	Homo sapiens	213-217
30940652-0	2019	Targeting CD38 Enhances the Antileukemic Activity of Ibrutinib in Chronic Lymphocytic Leukemia.	ibrutinib	53-62	CD38 molecule	Homo sapiens	10-14
31108259-1	2019	Ibrutinib (IBR), an irreversible Bruton"s tyrosine kinase (BTK) inhibitor, is expected to be a potent therapeutic modality, given that BTK is overexpressed in tumor-associated macrophages (TAMs) and participates in promoting tumor progression, angiogenesis, and immunosuppression.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	33-57
31108259-1	2019	Ibrutinib (IBR), an irreversible Bruton"s tyrosine kinase (BTK) inhibitor, is expected to be a potent therapeutic modality, given that BTK is overexpressed in tumor-associated macrophages (TAMs) and participates in promoting tumor progression, angiogenesis, and immunosuppression.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	59-62
31108259-1	2019	Ibrutinib (IBR), an irreversible Bruton"s tyrosine kinase (BTK) inhibitor, is expected to be a potent therapeutic modality, given that BTK is overexpressed in tumor-associated macrophages (TAMs) and participates in promoting tumor progression, angiogenesis, and immunosuppression.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	135-138
30957227-0	2019	Ibrutinib enhances the efficacy of ROR1 bispecific T cell engager mediated cytotoxicity in chronic lymphocytic leukaemia.	ibrutinib	0-9	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	35-39
31247078-2	2019	SUMMARY ANSWER: Skewing activated B cells toward regulatory B cells (Bregs) by Bruton"s tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect.	ibrutinib	127-136	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	79-103
31247078-2	2019	SUMMARY ANSWER: Skewing activated B cells toward regulatory B cells (Bregs) by Bruton"s tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect.	ibrutinib	127-136	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	105-108
31247078-2	2019	SUMMARY ANSWER: Skewing activated B cells toward regulatory B cells (Bregs) by Bruton"s tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect.	ibrutinib	127-136	membrane-spanning 4-domains, subfamily A, member 1	Mus musculus	217-221
31247078-4	2019	STUDY DESIGN, SIZE, DURATION: This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation.	ibrutinib	205-214	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	191-194
31247078-8	2019	MAIN RESULTS AND THE ROLE OF CHANCE: Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis.	ibrutinib	51-60	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	37-40
31247078-8	2019	MAIN RESULTS AND THE ROLE OF CHANCE: Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis.	ibrutinib	51-60	prostaglandin-endoperoxide synthase 2	Mus musculus	113-129
31247078-9	2019	In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinib-treated mice compared to anti-CD20 and control mice.	ibrutinib	80-89	membrane-spanning 4-domains, subfamily A, member 1	Mus musculus	120-124
31278310-10	2019	Moreover, simultaneous inhibition of PTK6 by ibrutinib and miR-214 significantly reduced cell proliferation/survival.	ibrutinib	45-54	protein tyrosine kinase 6	Homo sapiens	37-41
31108259-8	2019	STATEMENT OF SIGNIFICANCE: Ibrutinib (IBR), an irreversible Bruton"s tyrosine kinase (BTK) inhibitor, is expected to be a potent therapeutic modality, given that BTK is overexpressed in tumor-associated macrophages (TAMs) and participates in promoting tumor progression, angiogenesis, and immunosuppression.	ibrutinib	27-36	Bruton tyrosine kinase	Homo sapiens	60-84
31108259-8	2019	STATEMENT OF SIGNIFICANCE: Ibrutinib (IBR), an irreversible Bruton"s tyrosine kinase (BTK) inhibitor, is expected to be a potent therapeutic modality, given that BTK is overexpressed in tumor-associated macrophages (TAMs) and participates in promoting tumor progression, angiogenesis, and immunosuppression.	ibrutinib	27-36	Bruton tyrosine kinase	Homo sapiens	86-89
31108259-8	2019	STATEMENT OF SIGNIFICANCE: Ibrutinib (IBR), an irreversible Bruton"s tyrosine kinase (BTK) inhibitor, is expected to be a potent therapeutic modality, given that BTK is overexpressed in tumor-associated macrophages (TAMs) and participates in promoting tumor progression, angiogenesis, and immunosuppression.	ibrutinib	27-36	Bruton tyrosine kinase	Homo sapiens	162-165
31138459-1	2019	Since the approval of ibrutinib for the treatment of B-cell malignancies in 2012, numerous clinical trials have been reported using covalent inhibitors to target Bruton"s tyrosine kinase (BTK) for oncology indications.	ibrutinib	22-31	Bruton tyrosine kinase	Homo sapiens	162-186
30940652-8	2019	For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCgamma2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib.	ibrutinib	204-213	CD38 molecule	Homo sapiens	53-57
30940652-8	2019	For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCgamma2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib.	ibrutinib	204-213	CD38 molecule	Homo sapiens	97-101
30940652-8	2019	For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCgamma2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib.	ibrutinib	204-213	spleen associated tyrosine kinase	Homo sapiens	116-119
30940652-8	2019	For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCgamma2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib.	ibrutinib	204-213	Bruton tyrosine kinase	Homo sapiens	121-124
30940652-8	2019	For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCgamma2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib.	ibrutinib	204-213	phospholipase C gamma 2	Homo sapiens	126-135
30940652-8	2019	For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCgamma2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib.	ibrutinib	204-213	mitogen-activated protein kinase 3	Homo sapiens	137-143
30940652-8	2019	For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCgamma2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib.	ibrutinib	204-213	AKT serine/threonine kinase 1	Homo sapiens	149-152
30468254-1	2019	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has been shown to be highly effective in patients with chronic lymphocytic leukemia (CLL) and is approved for CLL treatment.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
30696950-0	2019	Ibrutinib reprograms the glucocorticoid receptor in chronic lymphocytic leukemia cells.	ibrutinib	0-9	nuclear receptor subfamily 3 group C member 1	Homo sapiens	25-48
30696950-4	2019	Ibrutinib increased transcription of the GR-signature gene GILZ in circulating CLL cells along with GR(pS211)/GR(pS226) ratios and lytic sensitivity to DEX that were not reversed by the competitive antagonist mifepristone in vitro.	ibrutinib	0-9	TSC22 domain family member 3	Homo sapiens	59-63
30963600-5	2019	Studies focusing on mutational dynamics and clonal evolution on Bruton"s tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53, BIRC3, CDKN2A, MAP3K14, NOTCH2, NSD2, and SMARCA4 genes.	ibrutinib	107-116	Bruton tyrosine kinase	Homo sapiens	64-88
31028669-1	2019	PURPOSE OF REVIEW: While the Bruton"s tyrosine kinase inhibitor (BTKi) ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL), current limitations include off-target toxicities and the development of resistance.	ibrutinib	71-80	Bruton tyrosine kinase	Homo sapiens	29-53
31028669-1	2019	PURPOSE OF REVIEW: While the Bruton"s tyrosine kinase inhibitor (BTKi) ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL), current limitations include off-target toxicities and the development of resistance.	ibrutinib	71-80	inhibitor of Bruton tyrosine kinase	Homo sapiens	65-69
31082751-3	2019	The Bruton"s Tyrosine Kinase inhibitor, Ibrutinib is used in the management of haematological malignancies and another Bruton"s Tyrosine Kinase inhibitor, ONO-4059 (also known as tirabrutinib), is in clinical development.	ibrutinib	40-49	Bruton tyrosine kinase	Homo sapiens	4-28
31082751-11	2019	CONCLUSION: The Bruton"s Tyrosine Kinase inhibitors, Ibrutinib and ONO-4059, show further inhibition of platelet aggregation in blood samples from patients with acute myocardial infarction, receiving dual antiplatelet therapy in a dose dependent manner.	ibrutinib	53-62	Bruton tyrosine kinase	Homo sapiens	16-40
31028669-0	2019	Targeting BTK in CLL: Beyond Ibrutinib.	ibrutinib	29-38	Bruton tyrosine kinase	Homo sapiens	10-13
30468254-1	2019	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has been shown to be highly effective in patients with chronic lymphocytic leukemia (CLL) and is approved for CLL treatment.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
30468254-2	2019	Unfortunately, resistance and intolerance to ibrutinib has been observed in several studies, opening the door for more specific BTK inhibitors.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	128-131
30901302-10	2019	In patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS (HR, 0.579), PFS (HR, 0.556), and OS (HR, 0.330) and slightly increased serious adverse events (35.7% v 28.6%), but the proportion of patients receiving at least six cycles of R-CHOP was similar between treatment arms (92.9% v 93.0%).	ibrutinib	39-48	DNA damage inducible transcript 3	Homo sapiens	252-256
30862686-3	2019	We performed genomic, metabolomic, and fluxomic analyses to evaluate the mechanism of action of the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib (IBR) in mantle cell lymphoma (MCL) cells.	ibrutinib	141-150	Bruton tyrosine kinase	Homo sapiens	100-124
30862686-3	2019	We performed genomic, metabolomic, and fluxomic analyses to evaluate the mechanism of action of the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib (IBR) in mantle cell lymphoma (MCL) cells.	ibrutinib	141-150	Bruton tyrosine kinase	Homo sapiens	126-129
30693983-0	2019	The HDAC6-selective inhibitor is effective against non-Hodgkin lymphoma and synergizes with ibrutinib in follicular lymphoma.	ibrutinib	92-101	histone deacetylase 6	Homo sapiens	4-9
30693983-4	2019	We investigated the efficacy of the histone deacetylase 6 (HDAC6) inhibitor A452 combined with a Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib on NHL and the underlying mechanisms compared with the current clinically tested HDAC6 inhibitor ACY-1215.	ibrutinib	138-147	Bruton tyrosine kinase	Homo sapiens	123-126
30901302-11	2019	In patients age 60 years or older, ibrutinib plus R-CHOP worsened EFS, PFS, and OS, increased serious adverse events (63.4% v 38.2%), and decreased the proportion of patients receiving at least six cycles of R-CHOP (73.7% v 88.8%).	ibrutinib	35-44	DNA damage inducible transcript 3	Homo sapiens	210-214
30901302-14	2019	In patients age 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes.	ibrutinib	35-44	DNA damage inducible transcript 3	Homo sapiens	122-126
31088809-1	2019	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib improves patient outcomes in chronic lymphocytic leukemia (CLL); however, some patients experience adverse events (AEs) leading to discontinuation.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	4-26
31088809-1	2019	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib improves patient outcomes in chronic lymphocytic leukemia (CLL); however, some patients experience adverse events (AEs) leading to discontinuation.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	28-31
31031187-1	2019	Ibrutinib (IB) is an oral Bruton"s tyrosine kinase (BTK) inhibitor that has demonstrated benefit in B cell cancers, but is associated with a dramatic increase in atrial fibrillation (AF).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	26-50
31031187-1	2019	Ibrutinib (IB) is an oral Bruton"s tyrosine kinase (BTK) inhibitor that has demonstrated benefit in B cell cancers, but is associated with a dramatic increase in atrial fibrillation (AF).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	52-55
31031187-1	2019	Ibrutinib (IB) is an oral Bruton"s tyrosine kinase (BTK) inhibitor that has demonstrated benefit in B cell cancers, but is associated with a dramatic increase in atrial fibrillation (AF).	ibrutinib	11-13	Bruton tyrosine kinase	Homo sapiens	26-50
31031187-1	2019	Ibrutinib (IB) is an oral Bruton"s tyrosine kinase (BTK) inhibitor that has demonstrated benefit in B cell cancers, but is associated with a dramatic increase in atrial fibrillation (AF).	ibrutinib	11-13	Bruton tyrosine kinase	Homo sapiens	52-55
30842083-6	2019	The PFS benefit with ibrutinib was independent of baseline risk factors, although patients with >=2 prior therapies had shorter PFS than those with <2 prior therapies, and the presence of TP53 or SF3B1 mutations showed a trend toward shorter PFS vs without these factors.	ibrutinib	21-30	tumor protein p53	Homo sapiens	188-192
30842083-6	2019	The PFS benefit with ibrutinib was independent of baseline risk factors, although patients with >=2 prior therapies had shorter PFS than those with <2 prior therapies, and the presence of TP53 or SF3B1 mutations showed a trend toward shorter PFS vs without these factors.	ibrutinib	21-30	splicing factor 3b subunit 1	Homo sapiens	196-201
30916599-4	2019	Areas covered: Ibrutinib is an oral irreversible inhibitor of Bruton"s tyrosine kinase, a mediator of B-cell receptor signaling, which plays a vital role in various B-cell neoplasms.	ibrutinib	15-24	Bruton tyrosine kinase	Homo sapiens	62-86
30814061-0	2019	Ibrutinib therapy downregulates AID enzyme and proliferative fractions in chronic lymphocytic leukemia.	ibrutinib	0-9	activation induced cytidine deaminase	Homo sapiens	32-35
30814061-4	2019	Recent preclinical data suggested that ibrutinib and idelalisib, 2 clinically approved kinase inhibitors, increase AID expression and genomic instability in normal and neoplastic B cells.	ibrutinib	39-48	activation induced cytidine deaminase	Homo sapiens	115-118
30814061-7	2019	We found that ibrutinib decreases the CLL PFs and, interestingly, also reduces AID expression, which correlates with dampened AKT and Janus Kinase 1 signaling.	ibrutinib	14-23	activation induced cytidine deaminase	Homo sapiens	79-82
30814061-7	2019	We found that ibrutinib decreases the CLL PFs and, interestingly, also reduces AID expression, which correlates with dampened AKT and Janus Kinase 1 signaling.	ibrutinib	14-23	AKT serine/threonine kinase 1	Homo sapiens	126-129
30814061-7	2019	We found that ibrutinib decreases the CLL PFs and, interestingly, also reduces AID expression, which correlates with dampened AKT and Janus Kinase 1 signaling.	ibrutinib	14-23	Janus kinase 1	Homo sapiens	134-148
30814061-8	2019	Moreover, although ibrutinib increases AID expression in a CLL cell line, it is unable to do so in primary CLL samples.	ibrutinib	19-28	activation induced cytidine deaminase	Homo sapiens	39-42
30814061-9	2019	Our results uncover a differential response to ibrutinib between cell lines and the CLL clone and imply that ibrutinib could differ from idelalisib in their potential to induce AID in treated patients.	ibrutinib	109-118	activation induced cytidine deaminase	Homo sapiens	177-180
31068440-3	2019	Through genomic analyses of clinical specimens, we show that metabolic reprogramming toward oxidative phosphorylation (OXPHOS) and glutaminolysis is associated with therapeutic resistance to the Bruton"s tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma (MCL), a B cell lymphoma subtype with poor clinical outcomes.	ibrutinib	230-239	Bruton tyrosine kinase	Homo sapiens	195-219
31076570-4	2019	Ibrutinib, an oral inhibitor of the Bruton"s tyrosine kinase (BTK) has proved to be remarkably efficient against treatment naive (TN), heavily pre-treated and high-risk chronic lymphocytic leukaemia (CLL), with limited adverse events.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	36-60
31076570-4	2019	Ibrutinib, an oral inhibitor of the Bruton"s tyrosine kinase (BTK) has proved to be remarkably efficient against treatment naive (TN), heavily pre-treated and high-risk chronic lymphocytic leukaemia (CLL), with limited adverse events.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	62-65
31044267-1	2019	INTRODUCTION: In the HELIOS trial, bendamustine/rituximab (BR) plus ibrutinib (BR-I) improved disease outcomes versus BR plus placebo in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma.	ibrutinib	68-77	IKAROS family zinc finger 2	Homo sapiens	21-27
31025232-13	2019	An irreversible inhibitor of ITK, ibrutinib, blocked ex vivo Th17 generation and IL-17A production, conversely augmented FOXP3 expression only at low doses in Treg cultures.	ibrutinib	34-43	IL2 inducible T cell kinase	Homo sapiens	29-32
31025232-13	2019	An irreversible inhibitor of ITK, ibrutinib, blocked ex vivo Th17 generation and IL-17A production, conversely augmented FOXP3 expression only at low doses in Treg cultures.	ibrutinib	34-43	interleukin 17A	Homo sapiens	81-87
31025232-13	2019	An irreversible inhibitor of ITK, ibrutinib, blocked ex vivo Th17 generation and IL-17A production, conversely augmented FOXP3 expression only at low doses in Treg cultures.	ibrutinib	34-43	forkhead box P3	Homo sapiens	121-126
30760494-0	2019	Targeting Thioredoxin Reductase by Ibrutinib Promotes Apoptosis of SMMC-7721 Cells.	ibrutinib	35-44	peroxiredoxin 5	Homo sapiens	10-31
30760494-1	2019	Ibrutinib (IBT), the first-in-class inhibitor of Bruton"s tyrosine kinase (BTK), has demonstrated clinical activity against various B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	49-73
30760494-1	2019	Ibrutinib (IBT), the first-in-class inhibitor of Bruton"s tyrosine kinase (BTK), has demonstrated clinical activity against various B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	75-78
30760494-1	2019	Ibrutinib (IBT), the first-in-class inhibitor of Bruton"s tyrosine kinase (BTK), has demonstrated clinical activity against various B-cell malignancies.	ibrutinib	11-14	Bruton tyrosine kinase	Homo sapiens	49-73
30760494-1	2019	Ibrutinib (IBT), the first-in-class inhibitor of Bruton"s tyrosine kinase (BTK), has demonstrated clinical activity against various B-cell malignancies.	ibrutinib	11-14	Bruton tyrosine kinase	Homo sapiens	75-78
30760494-3	2019	Our study revealed that IBT can inhibit SMMC-7721 cells through irreversible inhibition of mammalian thioredoxin reductase enzymes.	ibrutinib	24-27	peroxiredoxin 5	Homo sapiens	101-122
31044267-0	2019	Systemic Exposure of Rituximab Increased by Ibrutinib: Pharmacokinetic Results and Modeling Based on the HELIOS Trial.	ibrutinib	44-53	IKAROS family zinc finger 2	Homo sapiens	105-111
30938714-8	2019	Ex vivo expansion of T-cells and proportions of CD4+/CD8+ CAR T-cells with CD62L+CD127+ immunophenotype were significantly greater in patients on ibrutinib at leukapheresis.	ibrutinib	146-155	CD4 molecule	Homo sapiens	48-51
31013298-7	2019	A preclinical study of ibrutinib, a small molecule inhibitor of mouse and human ITK, in established lymphoma was carried out and showed lymphoma regression in 8/12 (67%) mice.	ibrutinib	23-32	IL2 inducible T cell kinase	Homo sapiens	80-83
30373751-3	2019	Therapeutic targeting of sIgM function via ibrutinib, an inhibitor of Bruton tyrosine kinase (BTK), causes inhibition and tumor cell redistribution into the blood, with significant clinical benefit.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	70-92
30373751-3	2019	Therapeutic targeting of sIgM function via ibrutinib, an inhibitor of Bruton tyrosine kinase (BTK), causes inhibition and tumor cell redistribution into the blood, with significant clinical benefit.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	94-97
30938714-8	2019	Ex vivo expansion of T-cells and proportions of CD4+/CD8+ CAR T-cells with CD62L+CD127+ immunophenotype were significantly greater in patients on ibrutinib at leukapheresis.	ibrutinib	146-155	CD8a molecule	Homo sapiens	53-56
30938714-8	2019	Ex vivo expansion of T-cells and proportions of CD4+/CD8+ CAR T-cells with CD62L+CD127+ immunophenotype were significantly greater in patients on ibrutinib at leukapheresis.	ibrutinib	146-155	CXADR pseudogene 1	Homo sapiens	58-61
30938714-8	2019	Ex vivo expansion of T-cells and proportions of CD4+/CD8+ CAR T-cells with CD62L+CD127+ immunophenotype were significantly greater in patients on ibrutinib at leukapheresis.	ibrutinib	146-155	selectin L	Homo sapiens	75-80
30938714-8	2019	Ex vivo expansion of T-cells and proportions of CD4+/CD8+ CAR T-cells with CD62L+CD127+ immunophenotype were significantly greater in patients on ibrutinib at leukapheresis.	ibrutinib	146-155	interleukin 7 receptor	Homo sapiens	81-86
31188814-2	2019	MCL relies upon B-cell receptor signaling through Bruton tyrosine kinase (BTK); therefore, the development of the BTK inhibitors ibrutinib and acalabrutinib represents a therapeutic breakthrough.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	50-72
30907011-2	2019	Currently, Bruton tyrosine kinase (BTK) inhibitor (ibrutinib) is one of the most promising medicine in clinical trials for DLBCL, to which about 25% of patients with relapsed or refractory DLBCL are responsive.	ibrutinib	51-60	Bruton tyrosine kinase	Homo sapiens	11-33
30907011-2	2019	Currently, Bruton tyrosine kinase (BTK) inhibitor (ibrutinib) is one of the most promising medicine in clinical trials for DLBCL, to which about 25% of patients with relapsed or refractory DLBCL are responsive.	ibrutinib	51-60	Bruton tyrosine kinase	Homo sapiens	35-38
30907011-7	2019	Notably, ibrutinib-resistant DLBCL cells also respond to TAK1 inhibition.	ibrutinib	9-18	mitogen-activated protein kinase kinase kinase 7	Homo sapiens	57-61
30907011-16	2019	Importantly, TAK1 inhibition overcomes ibrutinib resistance in DLBCL cells.	ibrutinib	39-48	mitogen-activated protein kinase kinase kinase 7	Homo sapiens	13-17
31188814-2	2019	MCL relies upon B-cell receptor signaling through Bruton tyrosine kinase (BTK); therefore, the development of the BTK inhibitors ibrutinib and acalabrutinib represents a therapeutic breakthrough.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	74-77
31188814-2	2019	MCL relies upon B-cell receptor signaling through Bruton tyrosine kinase (BTK); therefore, the development of the BTK inhibitors ibrutinib and acalabrutinib represents a therapeutic breakthrough.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	114-117
30878129-2	2019	Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue.	ibrutinib	0-9	inhibitor of Bruton tyrosine kinase	Homo sapiens	36-68
30878129-2	2019	Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue.	ibrutinib	0-9	inhibitor of Bruton tyrosine kinase	Homo sapiens	70-74
30878129-2	2019	Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	70-73
30888232-8	2019	In 2013, ibrutinib was approved by the FDA as the first-in-class BTK inhibitors for the treatment of mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), and now it is also undergoing clinical evaluation for other indications in either single or combined therapy.	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	65-68
31043832-3	2019	The Bruton tyrosine kinase (btk) inhibitor ibrutinib has proven to be an effective agent for patients with r/r mcl.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	4-26
31043832-3	2019	The Bruton tyrosine kinase (btk) inhibitor ibrutinib has proven to be an effective agent for patients with r/r mcl.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	28-31
30988561-1	2019	Ibrutinib is the only approved novel agent that is available for the treatment of relapsed-refractory and treatment-naive chronic lymphocytic leukemia patients with deletion 17p or TP53 mutation in India.	ibrutinib	0-9	tumor protein p53	Homo sapiens	181-185
31043832-6	2019	Novel btk inhibitors such as acalabrutinib, zanubrutinib, and tirabrutinib are designed to improve on the safety and efficacy of first-generation btk inhibitors such as ibrutinib.	ibrutinib	169-178	Bruton tyrosine kinase	Homo sapiens	6-9
31043832-6	2019	Novel btk inhibitors such as acalabrutinib, zanubrutinib, and tirabrutinib are designed to improve on the safety and efficacy of first-generation btk inhibitors such as ibrutinib.	ibrutinib	169-178	Bruton tyrosine kinase	Homo sapiens	146-149
30638402-3	2019	Areas covered: Ibrutinib, the first-in-class BTK inhibitor registered for MCL therapy, is efficient, with clear benefits of its use.	ibrutinib	15-24	Bruton tyrosine kinase	Homo sapiens	45-48
30277101-1	2019	Increased absolute lymphocyte count (ALC) is a key feature of chronic lymphocytic leukemia (CLL) but is also observed during treatment with B-cell receptor pathway inhibitors including ibrutinib, a first-in-class inhibitor of Bruton"s tyrosine kinase.	ibrutinib	185-194	Bruton tyrosine kinase	Homo sapiens	226-250
30663221-0	2019	The Ibr-7 derivative of ibrutinib exhibits enhanced cytotoxicity against non-small cell lung cancer cells via targeting of mTORC1/S6 signaling.	ibrutinib	24-33	CREB regulated transcription coactivator 1	Mus musculus	123-129
30663221-1	2019	Ibrutinib is a small molecule drug that targets Bruton"s tyrosine kinase in B-cell malignancies and is highly efficient at killing mantle cell lymphoma and chronic lymphocytic leukemia.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	48-72
30927175-3	2019	Ibrutinib was the first orally available, nonselective and irreversible inhibitor of BTK approved for the treatment of patients with various B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	85-88
30807093-1	2019	The impact of covalent binding on PROTAC-mediated degradation of BTK was investigated through the preparation of both covalent binding and reversible binding PROTACs derived from the covalent BTK inhibitor ibrutinib.	ibrutinib	206-215	Bruton tyrosine kinase	Homo sapiens	65-68
30559170-10	2019	FOXO1 activity was further significantly enhanced on combining AZD8055 with ibrutinib.	ibrutinib	76-85	forkhead box O1	Mus musculus	0-5
30559170-11	2019	CONCLUSIONS: Our studies demonstrate that dual mTOR inhibitors show promise as future CLL therapies, particularly in combination with ibrutinib.	ibrutinib	134-143	mechanistic target of rapamycin kinase	Mus musculus	47-51
30692684-1	2019	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has substantially improved therapeutic options for chronic lymphocytic leukemia (CLL).	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	4-26
30700840-3	2019	The functional relevance of BTK for lymphoid malignancies is strongly supported by the observation that resistance to therapy in CLL patients treated with BTK inhibitors such as ibrutinib is often associated with mutations in genes coding for BTK or Phospholipase-C gamma (PLCgamma).	ibrutinib	178-187	Bruton tyrosine kinase	Homo sapiens	28-31
30700840-3	2019	The functional relevance of BTK for lymphoid malignancies is strongly supported by the observation that resistance to therapy in CLL patients treated with BTK inhibitors such as ibrutinib is often associated with mutations in genes coding for BTK or Phospholipase-C gamma (PLCgamma).	ibrutinib	178-187	Bruton tyrosine kinase	Homo sapiens	155-158
30700840-3	2019	The functional relevance of BTK for lymphoid malignancies is strongly supported by the observation that resistance to therapy in CLL patients treated with BTK inhibitors such as ibrutinib is often associated with mutations in genes coding for BTK or Phospholipase-C gamma (PLCgamma).	ibrutinib	178-187	Bruton tyrosine kinase	Homo sapiens	155-158
30742126-6	2019	By examining cell signaling on this map, we rationally selected ibrutinib, a BTK and ITK inhibitor, and administered it before T cell activation to direct differentiation toward a T stem cell memory (TSCM)-like phenotype.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	77-80
30742126-6	2019	By examining cell signaling on this map, we rationally selected ibrutinib, a BTK and ITK inhibitor, and administered it before T cell activation to direct differentiation toward a T stem cell memory (TSCM)-like phenotype.	ibrutinib	64-73	IL2 inducible T cell kinase	Homo sapiens	85-88
30692684-1	2019	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has substantially improved therapeutic options for chronic lymphocytic leukemia (CLL).	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	28-31
30692684-5	2019	Specifically, we observed and validated preferential sensitivity to proteasome, PLK1, and mTOR inhibitors during ibrutinib treatment.	ibrutinib	113-122	polo like kinase 1	Homo sapiens	80-84
30692684-5	2019	Specifically, we observed and validated preferential sensitivity to proteasome, PLK1, and mTOR inhibitors during ibrutinib treatment.	ibrutinib	113-122	mechanistic target of rapamycin kinase	Homo sapiens	90-94
30791947-2	2019	Dual targeting BTK and BCL2 with ibrutinib and venetoclax has improved outcomes in MCL patients who were predicted not to respond to conventional therapy, but it is unlikely to be curative.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	15-18
30685871-10	2019	In conclusion, low blood concentrations of ibrutinib and the novel Btk inhibitors suffice for GPVI selective platelet inhibition relevant for atherothrombosis but do not impair primary haemostasis.	ibrutinib	43-52	glycoprotein VI platelet	Homo sapiens	94-98
30545835-1	2019	The covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is highly efficacious against multiple B-cell malignancies.	ibrutinib	52-61	Bruton tyrosine kinase	Homo sapiens	13-35
30545835-1	2019	The covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is highly efficacious against multiple B-cell malignancies.	ibrutinib	52-61	Bruton tyrosine kinase	Homo sapiens	37-40
30791947-2	2019	Dual targeting BTK and BCL2 with ibrutinib and venetoclax has improved outcomes in MCL patients who were predicted not to respond to conventional therapy, but it is unlikely to be curative.	ibrutinib	33-42	BCL2 apoptosis regulator	Homo sapiens	23-27
30508305-3	2019	METHODS: Using targeted deep sequencing, mutations in 29 genes associated with CLL and/or the BCR signaling pathway were assessed in patients with CLL who developed resistance to BTK inhibition with ibrutinib/acalabrutinib at a single institution.	ibrutinib	199-208	Bruton tyrosine kinase	Homo sapiens	179-182
30423172-3	2019	Agents like the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs (IMiDs) like pomalidomide and lenalidomide have shown promising high response rates in the salvage setting.	ibrutinib	55-64	Bruton tyrosine kinase	Homo sapiens	16-38
30423172-3	2019	Agents like the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs (IMiDs) like pomalidomide and lenalidomide have shown promising high response rates in the salvage setting.	ibrutinib	55-64	Bruton tyrosine kinase	Homo sapiens	40-43
30777096-5	2019	Here, for the first time, we investigate whether the combination of PKCbeta inhibitor enzastaurin and BTK inhibitor ibrutinib has synergistic anti-tumor effects in DLBCL.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	102-105
30777096-13	2019	Co-treatment with low doses of enzastaurin and ibrutinib could effectively downregulate BCR, NF-kappaB, JAK and MAPK related signaling pathway.	ibrutinib	47-56	BCR activator of RhoGEF and GTPase	Homo sapiens	88-91
30723172-2	2019	Ibrutinib, a drug that inhibits Bruton"s tyrosine kinase (BTK), has improved the overall survival of patients with MCL; however, resistance to ibrutinib has emerged as a decisive, negative factor in the prognosis of MCL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	32-56
30737226-0	2019	Anti-BAFF-R antibody VAY-736 demonstrates promising preclinical activity in CLL and enhances effectiveness of ibrutinib.	ibrutinib	110-119	tumor necrosis factor receptor superfamily, member 13c	Mus musculus	5-11
30737226-1	2019	The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib has transformed chronic lymphocytic leukemia (CLL) therapy but requires continuous administration.	ibrutinib	44-53	inhibitor of Bruton agammaglobulinemia tyrosine kinase	Mus musculus	4-36
30737226-1	2019	The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib has transformed chronic lymphocytic leukemia (CLL) therapy but requires continuous administration.	ibrutinib	44-53	inhibitor of Bruton agammaglobulinemia tyrosine kinase	Mus musculus	38-42
30737226-4	2019	Whereas CD20 antigen density on CLL cells decreases during ibrutinib treatment, the B-cell activating factor (BAFF) and its receptor (BAFF-R) remain elevated.	ibrutinib	59-68	membrane-spanning 4-domains, subfamily A, member 1	Mus musculus	8-12
30737226-10	2019	Collectively, our findings support targeting the BAFF signaling pathway with VAY-736 to more effectively treat CLL as a single agent and in combination with ibrutinib.	ibrutinib	157-166	tumor necrosis factor (ligand) superfamily, member 13b	Mus musculus	49-53
30723172-2	2019	Ibrutinib, a drug that inhibits Bruton"s tyrosine kinase (BTK), has improved the overall survival of patients with MCL; however, resistance to ibrutinib has emerged as a decisive, negative factor in the prognosis of MCL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	58-61
30723172-2	2019	Ibrutinib, a drug that inhibits Bruton"s tyrosine kinase (BTK), has improved the overall survival of patients with MCL; however, resistance to ibrutinib has emerged as a decisive, negative factor in the prognosis of MCL.	ibrutinib	143-152	Bruton tyrosine kinase	Homo sapiens	58-61
30338509-0	2019	Unravelling the suboptimal response of TP53-mutated chronic lymphocytic leukaemia to ibrutinib.	ibrutinib	85-94	tumor protein p53	Homo sapiens	39-43
31723816-5	2019	Ibrutinib and idelalisib inhibit the Bruton tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) delta, respectively, thus interfering with supportive signals coming from the microenvironment via the BCR.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	37-59
31723816-5	2019	Ibrutinib and idelalisib inhibit the Bruton tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) delta, respectively, thus interfering with supportive signals coming from the microenvironment via the BCR.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	61-64
31723816-5	2019	Ibrutinib and idelalisib inhibit the Bruton tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) delta, respectively, thus interfering with supportive signals coming from the microenvironment via the BCR.	ibrutinib	0-9	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta	Homo sapiens	97-108
30706214-2	2019	The first-in-class BTK inhibitor ibrutinib is a small molecule drug that binds covalently to BTK and has been proved to be an effective treatment for various B-cell malignancies.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	19-22
30706214-2	2019	The first-in-class BTK inhibitor ibrutinib is a small molecule drug that binds covalently to BTK and has been proved to be an effective treatment for various B-cell malignancies.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	93-96
30338509-1	2019	TP53-disrupted chronic lymphocytic leukaemia (CLL) patients show a suboptimal long-term response to ibrutinib.	ibrutinib	100-109	tumor protein p53	Homo sapiens	0-4
30338509-2	2019	We hereby report that ibrutinib-induced in vitro apoptosis and proliferation inhibition were significantly lower in TP53-mutated (TP53-M) CLL cells compared to TP53 wild-type cells.	ibrutinib	22-31	tumor protein p53	Homo sapiens	116-120
30338509-2	2019	We hereby report that ibrutinib-induced in vitro apoptosis and proliferation inhibition were significantly lower in TP53-mutated (TP53-M) CLL cells compared to TP53 wild-type cells.	ibrutinib	22-31	tumor protein p53	Homo sapiens	130-134
30338509-2	2019	We hereby report that ibrutinib-induced in vitro apoptosis and proliferation inhibition were significantly lower in TP53-mutated (TP53-M) CLL cells compared to TP53 wild-type cells.	ibrutinib	22-31	tumor protein p53	Homo sapiens	130-134
30559058-0	2019	Aggressive Leukemic Non-Nodal Mantle Cell Lymphoma With P53 Gene Rearrangement/Mutation is Highly Responsive to Rituximab/Ibrutinib Combination Therapy.	ibrutinib	122-131	tumor protein p53	Homo sapiens	56-59
30733667-5	2019	Glioma stem cell (GSC) lines, isolated from glioblastoma multiforme (GBM), were treated with different concentrations of ibrutinib, a specific inhibitor of BTK, in order to evaluate their metabolic activity, mitotic index and mortality.	ibrutinib	121-130	Bruton tyrosine kinase	Homo sapiens	156-159
30381447-8	2019	Our data underscore the rationale of a number of recently opened clinical trials, such as ibrutinib in ERBB2- or ERBB4-expressing cancers.	ibrutinib	90-99	erb-b2 receptor tyrosine kinase 2	Homo sapiens	103-108
30381447-8	2019	Our data underscore the rationale of a number of recently opened clinical trials, such as ibrutinib in ERBB2- or ERBB4-expressing cancers.	ibrutinib	90-99	erb-b2 receptor tyrosine kinase 4	Homo sapiens	113-118
30381956-2	2019	To date, ibrutinib is the only Bruton tyrosine kinase (BTK) inhibitor that"s approved for treatment of CLL.	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	31-53
30381956-2	2019	To date, ibrutinib is the only Bruton tyrosine kinase (BTK) inhibitor that"s approved for treatment of CLL.	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	55-58
30567753-1	2019	Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase (BTK) and has shown single-agent activity in recurrent/refractory central nervous system (CNS) lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	43-65
30567753-1	2019	Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase (BTK) and has shown single-agent activity in recurrent/refractory central nervous system (CNS) lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	67-70
30646846-0	2019	Btk inhibitor ibrutinib reduces inflammatory myeloid cell responses in the lung during murine pneumococcal pneumonia.	ibrutinib	14-23	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	0-3
30498085-2	2019	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib effectively inhibits BCR-dependent proliferation and survival signals and has emerged as a breakthrough therapy for CLL.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
30498085-2	2019	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib effectively inhibits BCR-dependent proliferation and survival signals and has emerged as a breakthrough therapy for CLL.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
30646846-3	2019	Ibrutinib is an irreversible inhibitor of Bruton"s tyrosine kinase (Btk), a key signaling protein controlling the activation of various immune cells, including macrophages and neutrophils.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	42-66
30646846-3	2019	Ibrutinib is an irreversible inhibitor of Bruton"s tyrosine kinase (Btk), a key signaling protein controlling the activation of various immune cells, including macrophages and neutrophils.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	68-71
30646846-9	2019	In vitro, ibrutinib inhibited macrophage TNF secretion and neutrophil activation upon LTA and pneumococcal stimulation.	ibrutinib	10-19	tumor necrosis factor	Mus musculus	41-44
30646846-10	2019	CONCLUSIONS: Taken together, these data indicate that the Btk inhibitor ibrutinib reduces inflammatory myeloid cell responses during acute pulmonary inflammation evoked by LTA and antibiotic-treated pneumococcal pneumonia and suggest that ibrutinib has the potential to inhibit ongoing lung inflammation in an acute infectious setting.	ibrutinib	72-81	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	58-61
29977015-5	2019	Mutant-G-CSFR-expressing cells displayed enhanced sensitivity (3-5-fold lower IC50) for ibrutinib-based chemical inhibition of Btk.	ibrutinib	88-97	colony stimulating factor 3 receptor (granulocyte)	Mus musculus	7-13
30183082-8	2019	WM patients with TP53 mutations show response to ibrutinib.	ibrutinib	49-58	tumor protein p53	Homo sapiens	17-21
29977015-5	2019	Mutant-G-CSFR-expressing cells displayed enhanced sensitivity (3-5-fold lower IC50) for ibrutinib-based chemical inhibition of Btk.	ibrutinib	88-97	Bruton tyrosine kinase	Homo sapiens	127-130
29977015-9	2019	Altogether, these data demonstrate the strength of unsupervised proteomics analyses in dissecting oncogenic pathways, and suggest repositioning Ibrutinib for therapy of myeloid leukemia bearing CSF3R mutations.	ibrutinib	144-153	colony stimulating factor 3 receptor	Homo sapiens	194-199
30455436-6	2019	Functional modeling demonstrated that compromise of the SWI-SNF complex facilitated transcriptional upregulation of BCL2L1 (Bcl-xL) providing a selective advantage against ibrutinib plus venetoclax.	ibrutinib	172-181	BCL2 like 1	Homo sapiens	116-122
31478435-9	2019	Subsequently, Btk inhibitor, ibrutinib, suppressed GSC generation and stemness markers.	ibrutinib	29-38	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	14-17
30573111-1	2018	Ibrutinib, a novel and potent Bruton tyrosine kinase inhibitor, is an effective and well-tolerated treatment for a variety of B-cell lymphomas.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	30-52
31230047-0	2019	A Phase 1b/2 Study of the Bruton Tyrosine Kinase Inhibitor Ibrutinib and the PD-L1 Inhibitor Durvalumab in Patients with Pretreated Solid Tumors.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	26-48
30647852-5	2018	We detected sustained overexpression of Axl in CLL B-cells from CLL patients on ibrutinib treatment, suggests targeting Axl could be a promising strategy to overcome drug resistance and killing of CLL B-cells in these patients.	ibrutinib	80-89	AXL receptor tyrosine kinase	Homo sapiens	120-123
30026342-0	2018	Inhibition of Btk by Btk-specific concentrations of ibrutinib and acalabrutinib delays but does not block platelet aggregation mediated by glycoprotein VI.	ibrutinib	52-61	Bruton tyrosine kinase	Homo sapiens	14-17
30026342-0	2018	Inhibition of Btk by Btk-specific concentrations of ibrutinib and acalabrutinib delays but does not block platelet aggregation mediated by glycoprotein VI.	ibrutinib	52-61	Bruton tyrosine kinase	Homo sapiens	21-24
30026342-1	2018	Ibrutinib and acalabrutinib are irreversible inhibitors of Bruton tyrosine kinase used in the treatment of B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	59-81
30026342-3	2018	In the present study, we demonstrate that concentrations of ibrutinib and acalabrutinib that block Bruton tyrosine kinase activity, as shown by loss of phosphorylation at tyrosine 223 and phospholipase C-gamma2, delay but do not block aggregation in response to a maximally-effective concentration of collagen-related peptide or collagen.	ibrutinib	60-69	Bruton tyrosine kinase	Homo sapiens	99-121
30026342-3	2018	In the present study, we demonstrate that concentrations of ibrutinib and acalabrutinib that block Bruton tyrosine kinase activity, as shown by loss of phosphorylation at tyrosine 223 and phospholipase C-gamma2, delay but do not block aggregation in response to a maximally-effective concentration of collagen-related peptide or collagen.	ibrutinib	60-69	phospholipase C gamma 2	Homo sapiens	188-210
30026342-5	2018	Ex vivo studies on patients treated with ibrutinib, but not acalabrutinib, showed a reduction of platelet aggregation in response to collagen-related peptide indicating that the clinical dose of ibrutinib but not acalabrutinib is supramaximal for Bruton tyrosine kinase blockade.	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	247-269
30026342-6	2018	Unexpectedly, low concentrations of ibrutinib inhibited aggregation in response to collagen-related peptide in patients deficient in Bruton tyrosine kinase.	ibrutinib	36-45	Bruton tyrosine kinase	Homo sapiens	133-155
29912596-5	2018	In this review, we will discuss the currently most active two drugs: ibrutinib and venetoclax, both of which have shown high response rates in R/R MCL.	ibrutinib	69-78	C-type lectin domain family 4 member D	Homo sapiens	147-150
30510142-0	2018	XPO1 Inhibitor Selinexor Overcomes Intrinsic Ibrutinib Resistance in Mantle Cell Lymphoma via Nuclear Retention of IkappaB.	ibrutinib	45-54	exportin 1	Homo sapiens	0-4
30500458-21	2019	Of the approximate three dozen FDA-approved small molecule protein kinase inhibitors, five are type VI irreversible inhibitors and four of them including afatinib, osimertinib, dacomitinib, and neratinib are directed against the ErbB family of receptors (ibrutinib is the fifth and it targets Bruton tyrosine kinase).	ibrutinib	255-264	epidermal growth factor receptor	Homo sapiens	229-233
30647852-0	2018	Chronic lymphocytic leukemia cells from ibrutinib treated patients are sensitive to Axl receptor tyrosine kinase inhibitor therapy.	ibrutinib	40-49	AXL receptor tyrosine kinase	Homo sapiens	84-87
30647852-3	2018	Ibrutinib-exposed CLL B-cells were treated with increasing doses (0.01- 0.50muM) of a new formulation of high-affinity Axl inhibitor, TP-0903 (tartrate salt), for 24 hours and LD50 doses were determined.	ibrutinib	0-9	AXL receptor tyrosine kinase	Homo sapiens	119-122
30647852-5	2018	We detected sustained overexpression of Axl in CLL B-cells from CLL patients on ibrutinib treatment, suggests targeting Axl could be a promising strategy to overcome drug resistance and killing of CLL B-cells in these patients.	ibrutinib	80-89	AXL receptor tyrosine kinase	Homo sapiens	40-43
30152528-0	2018	Biclonal IGHV-4-34 hairy cell leukemia variant and CLL - successful treatment with ibrutinib and venetoclax.	ibrutinib	83-92	immunoglobulin heavy variable 4-34	Homo sapiens	9-18
30527922-6	2018	Single agent treatment with the Btk-inhibitor ibrutinib is not only approved in relapsed CLL; but also for frontline therapy.	ibrutinib	46-55	Bruton tyrosine kinase	Homo sapiens	32-35
29846137-0	2018	A drug-drug interaction study of ibrutinib with moderate/strong CYP3A inhibitors in patients with B-cell malignancies.	ibrutinib	33-42	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	64-69
29846137-1	2018	This was an open-label, multicenter, phase-1 study to evaluate the drug interaction between steady-state ibrutinib and moderate (erythromycin) and strong (voriconazole) CYP3A inhibitors in patients with B-cell malignancies and to confirm dosing recommendations.	ibrutinib	105-114	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	169-174
30401751-2	2018	The BTK inhibitor ibrutinib is active in MYD88-mutated (MYD88 MUT ) WM patients, but shows lower activity in MYD88 wild-type (MYD88 WT ) disease.	ibrutinib	18-27	MYD88 innate immune signal transduction adaptor	Homo sapiens	56-61
30254130-2	2018	We previously demonstrated a decline in Bruton"s tyrosine kinase (BTK) protein levels in CLL cells after 1 cycle of ibrutinib, suggesting ibrutinib dose could be lowered after the first cycle without loss of biological effect.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	40-64
30254130-2	2018	We previously demonstrated a decline in Bruton"s tyrosine kinase (BTK) protein levels in CLL cells after 1 cycle of ibrutinib, suggesting ibrutinib dose could be lowered after the first cycle without loss of biological effect.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	66-69
30254130-2	2018	We previously demonstrated a decline in Bruton"s tyrosine kinase (BTK) protein levels in CLL cells after 1 cycle of ibrutinib, suggesting ibrutinib dose could be lowered after the first cycle without loss of biological effect.	ibrutinib	138-147	Bruton tyrosine kinase	Homo sapiens	40-64
30254130-2	2018	We previously demonstrated a decline in Bruton"s tyrosine kinase (BTK) protein levels in CLL cells after 1 cycle of ibrutinib, suggesting ibrutinib dose could be lowered after the first cycle without loss of biological effect.	ibrutinib	138-147	Bruton tyrosine kinase	Homo sapiens	66-69
30254130-7	2018	Plasma and intracellular levels of ibrutinib were dose-dependent, and even the lowest dose was sufficient to occupy, on average, more than 95% of BTK protein.	ibrutinib	35-44	Bruton tyrosine kinase	Homo sapiens	146-149
30254130-8	2018	In concert, BTK downstream signaling inhibition was maintained with 140 mg/d ibrutinib in cycle 3, and there were comparable reductions in total and phospho-BTK (Tyr223) protein levels across 3 cycles.	ibrutinib	77-86	Bruton tyrosine kinase	Homo sapiens	12-15
30401751-2	2018	The BTK inhibitor ibrutinib is active in MYD88-mutated (MYD88 MUT ) WM patients, but shows lower activity in MYD88 wild-type (MYD88 WT ) disease.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
30401751-2	2018	The BTK inhibitor ibrutinib is active in MYD88-mutated (MYD88 MUT ) WM patients, but shows lower activity in MYD88 wild-type (MYD88 WT ) disease.	ibrutinib	18-27	MYD88 innate immune signal transduction adaptor	Homo sapiens	41-46
30401751-2	2018	The BTK inhibitor ibrutinib is active in MYD88-mutated (MYD88 MUT ) WM patients, but shows lower activity in MYD88 wild-type (MYD88 WT ) disease.	ibrutinib	18-27	MYD88 innate immune signal transduction adaptor	Homo sapiens	56-61
30510142-1	2018	Inhibition of B-cell receptor (BCR) signaling through the BTK inhibitor, ibrutinib, has generated a remarkable response in mantle cell lymphoma (MCL).	ibrutinib	73-82	Bruton tyrosine kinase	Homo sapiens	58-61
30510142-8	2018	Furthermore, downregulation of the NFkappaB gene signature, as opposed to BCR signature, was a common feature that underlies the response of MCL to both selinexor and ibrutinib.	ibrutinib	167-176	nuclear factor kappa B subunit 1	Homo sapiens	35-43
30510142-9	2018	Meanwhile, unaltered NFkappaB was associated with ibrutinib resistance.	ibrutinib	50-59	nuclear factor kappa B subunit 1	Homo sapiens	21-29
30510142-13	2018	Our data highlight the role of NFkappaB pathway in drug response to ibrutinib and selinexor and show the potential of using selinexor to prevent and overcome intrinsic ibrutinib resistance through NFkappaB inhibition.	ibrutinib	68-77	nuclear factor kappa B subunit 1	Homo sapiens	31-39
30290988-2	2018	Several covalent irreversible inhibitors of Btk are currently in development including ibrutinib which was approved for treatment of B-cell malignancies.	ibrutinib	87-96	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	44-47
30429379-0	2018	Panobinostat acts synergistically with ibrutinib in diffuse large B cell lymphoma cells with MyD88 L265P mutations.	ibrutinib	39-48	MYD88 innate immune signal transduction adaptor	Homo sapiens	93-98
30401751-2	2018	The BTK inhibitor ibrutinib is active in MYD88-mutated (MYD88 MUT ) WM patients, but shows lower activity in MYD88 wild-type (MYD88 WT ) disease.	ibrutinib	18-27	MYD88 innate immune signal transduction adaptor	Homo sapiens	56-61
30401751-10	2018	The findings depict genomic and transcriptional events associated with MYD88 WT WM and provide mechanistic insights for disease transformation, decreased ibrutinib activity, and novel drug approaches for this population.	ibrutinib	154-163	MYD88 innate immune signal transduction adaptor	Homo sapiens	71-76
30247919-0	2018	P-Glycoprotein (MDR1/ABCB1) Restricts Brain Penetration of the Bruton"s Tyrosine Kinase Inhibitor Ibrutinib, While Cytochrome P450-3A (CYP3A) Limits Its Oral Bioavailability.	ibrutinib	98-107	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	16-20
30247919-6	2018	Abcb1 and/or Abcg2 did not obviously restrict ibrutinib oral bioavailability, but Cyp3a deficiency increased the ibrutinib plasma AUC by 9.7-fold compared to wild-type mice.	ibrutinib	113-122	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	82-87
30247919-0	2018	P-Glycoprotein (MDR1/ABCB1) Restricts Brain Penetration of the Bruton"s Tyrosine Kinase Inhibitor Ibrutinib, While Cytochrome P450-3A (CYP3A) Limits Its Oral Bioavailability.	ibrutinib	98-107	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	21-26
30247919-0	2018	P-Glycoprotein (MDR1/ABCB1) Restricts Brain Penetration of the Bruton"s Tyrosine Kinase Inhibitor Ibrutinib, While Cytochrome P450-3A (CYP3A) Limits Its Oral Bioavailability.	ibrutinib	98-107	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	63-87
30247919-1	2018	Ibrutinib (Imbruvica), an oral tyrosine kinase inhibitor (TKI) approved for treatment of B-cell malignancies, irreversibly inhibits the Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	136-160
30247919-1	2018	Ibrutinib (Imbruvica), an oral tyrosine kinase inhibitor (TKI) approved for treatment of B-cell malignancies, irreversibly inhibits the Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	162-165
30247919-1	2018	Ibrutinib (Imbruvica), an oral tyrosine kinase inhibitor (TKI) approved for treatment of B-cell malignancies, irreversibly inhibits the Bruton"s tyrosine kinase (BTK).	ibrutinib	11-20	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	136-160
30247919-1	2018	Ibrutinib (Imbruvica), an oral tyrosine kinase inhibitor (TKI) approved for treatment of B-cell malignancies, irreversibly inhibits the Bruton"s tyrosine kinase (BTK).	ibrutinib	11-20	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	162-165
30247919-2	2018	Its abundant metabolite, dihydrodiol-ibrutinib (ibrutinib-DiOH), which is primarily formed by CYP3A, has a 10-fold reduced BTK inhibitory activity.	ibrutinib	37-46	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	94-99
30247919-2	2018	Its abundant metabolite, dihydrodiol-ibrutinib (ibrutinib-DiOH), which is primarily formed by CYP3A, has a 10-fold reduced BTK inhibitory activity.	ibrutinib	37-46	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	123-126
30247919-3	2018	Using in vitro transport assays and genetically modified mouse models, we investigated whether the multidrug efflux transporters ABCB1 and ABCG2 and the multidrug-metabolizing CYP3A enzyme family can affect the oral bioavailability and tissue disposition of ibrutinib and ibrutinib-DiOH.	ibrutinib	258-267	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	129-134
30247919-3	2018	Using in vitro transport assays and genetically modified mouse models, we investigated whether the multidrug efflux transporters ABCB1 and ABCG2 and the multidrug-metabolizing CYP3A enzyme family can affect the oral bioavailability and tissue disposition of ibrutinib and ibrutinib-DiOH.	ibrutinib	258-267	ATP binding cassette subfamily G member 2 (Junior blood group)	Mus musculus	139-144
30247919-3	2018	Using in vitro transport assays and genetically modified mouse models, we investigated whether the multidrug efflux transporters ABCB1 and ABCG2 and the multidrug-metabolizing CYP3A enzyme family can affect the oral bioavailability and tissue disposition of ibrutinib and ibrutinib-DiOH.	ibrutinib	272-281	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	129-134
30247919-3	2018	Using in vitro transport assays and genetically modified mouse models, we investigated whether the multidrug efflux transporters ABCB1 and ABCG2 and the multidrug-metabolizing CYP3A enzyme family can affect the oral bioavailability and tissue disposition of ibrutinib and ibrutinib-DiOH.	ibrutinib	272-281	ATP binding cassette subfamily G member 2 (Junior blood group)	Mus musculus	139-144
30247919-4	2018	In vitro, ibrutinib was transported moderately by human ABCB1 and mouse Abcg2 but not detectably by human ABCG2.	ibrutinib	10-19	ATP binding cassette subfamily B member 1	Homo sapiens	56-61
30247919-4	2018	In vitro, ibrutinib was transported moderately by human ABCB1 and mouse Abcg2 but not detectably by human ABCG2.	ibrutinib	10-19	ATP binding cassette subfamily G member 2 (Junior blood group)	Mus musculus	72-77
30247919-5	2018	In mice, Abcb1 markedly restricted the brain penetration of ibrutinib and ibrutinib-DiOH, either alone or in combination with Abcg2, resulting in 4.5- and 5.9-fold increases in ibrutinib brain-to-plasma ratios in Abcb1a/1b-/- and Abcb1a/1b;Abcg2-/- mice relative to wild-type mice.	ibrutinib	60-69	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	9-14
30247919-5	2018	In mice, Abcb1 markedly restricted the brain penetration of ibrutinib and ibrutinib-DiOH, either alone or in combination with Abcg2, resulting in 4.5- and 5.9-fold increases in ibrutinib brain-to-plasma ratios in Abcb1a/1b-/- and Abcb1a/1b;Abcg2-/- mice relative to wild-type mice.	ibrutinib	74-83	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	9-14
30247919-5	2018	In mice, Abcb1 markedly restricted the brain penetration of ibrutinib and ibrutinib-DiOH, either alone or in combination with Abcg2, resulting in 4.5- and 5.9-fold increases in ibrutinib brain-to-plasma ratios in Abcb1a/1b-/- and Abcb1a/1b;Abcg2-/- mice relative to wild-type mice.	ibrutinib	74-83	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	9-14
30129285-8	2018	Relative to CIT studies that similarly excluded patients with del(17p) (CLL10) or enrolled older/less-fit patients (CLL11), PFS appeared favorable for ibrutinib in high-risk subgroups, including advanced disease, bulky lymph nodes, unmutated IGHV status, and presence of del(11q).	ibrutinib	151-160	immunoglobulin heavy variable 3-69-1 (pseudogene)	Homo sapiens	242-246
30247919-8	2018	Our results suggest that pharmacological inhibition of ABCB1 during ibrutinib therapy might benefit patients with malignancies or (micro)metastases positioned behind an intact blood-brain barrier, or with substantial expression of this transporter in the malignant cells.	ibrutinib	68-77	ATP binding cassette subfamily B member 1	Homo sapiens	55-60
30247919-9	2018	Moreover, given the strong in vivo impact of CYP3A, inhibitors or inducers of this enzyme family will likely strongly affect ibrutinib oral bioavailability and, thus, its therapeutic efficacy, as well as its toxicity risks.	ibrutinib	125-134	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	45-50
30385492-0	2018	Ibrutinib and Aspergillus: a Btk-targeted risk.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	29-32
30175400-8	2018	Overall, BTK mutations were observed in 17% patients after progression on ibrutinib.	ibrutinib	74-83	Bruton tyrosine kinase	Homo sapiens	9-12
30175400-12	2018	Demonstration of TP53 and NSD2 mutations in patients who developed blastoid transformation and ATM and TP53 mutations in patients who progressed, opens the door for future investigations in ibrutinib-refractory MCL.	ibrutinib	190-199	tumor protein p53	Homo sapiens	17-21
30021784-0	2018	Ibrutinib blocks Btk-dependent NF-kB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	17-20
29465264-2	2018	Here we show that, in CLL cells, the B-cell receptor (BCR) inhibitor ibrutinib reduced LPL mRNA and protein levels and inhibited FFA metabolism in vitro.	ibrutinib	69-78	lipoprotein lipase	Homo sapiens	87-90
30307543-7	2018	Furthermore, pretreatment of T1D PBMCs with ibrutinib, an inhibitor of Bruton tyrosine kinase, dampens EV-induced memory B cell activation and GAD65 antibody production.	ibrutinib	44-53	glutamate decarboxylase 2	Homo sapiens	143-148
30175400-12	2018	Demonstration of TP53 and NSD2 mutations in patients who developed blastoid transformation and ATM and TP53 mutations in patients who progressed, opens the door for future investigations in ibrutinib-refractory MCL.	ibrutinib	190-199	nuclear receptor binding SET domain protein 2	Homo sapiens	26-30
30175400-12	2018	Demonstration of TP53 and NSD2 mutations in patients who developed blastoid transformation and ATM and TP53 mutations in patients who progressed, opens the door for future investigations in ibrutinib-refractory MCL.	ibrutinib	190-199	ATM serine/threonine kinase	Homo sapiens	95-98
30175400-12	2018	Demonstration of TP53 and NSD2 mutations in patients who developed blastoid transformation and ATM and TP53 mutations in patients who progressed, opens the door for future investigations in ibrutinib-refractory MCL.	ibrutinib	190-199	tumor protein p53	Homo sapiens	103-107
30390220-4	2018	Discovery of the biological function of BTK and the development of covalent inhibitors for clinical use, ibrutinib as the lead agent and acalabrutinib as the second clinically approved BTK inhibitor, have revolutionized the treatment options for B-cell malignancies.	ibrutinib	105-114	Bruton tyrosine kinase	Homo sapiens	40-43
30280589-3	2018	To design novel effective and safety reversible BTK inhibitors, 115 newly cinnoline analogues were selected to perform molecular docking and 3D-QSAR study because of the main scaffold similarity to Ibrutinib.	ibrutinib	198-207	Bruton tyrosine kinase	Homo sapiens	48-51
30280589-2	2018	Ibrutinib is the most advanced irreversible BTK inhibitor for treating mantle cell lymphoma/chronic lymphocytic leukaemia but with existing drug resistance and adverse effects.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	44-47
30013190-7	2018	Furthermore, the BTK inhibitor ibrutinib can effectively inhibit the growth of neuroblastoma xenograft in nude mice, and the combination of ibrutinib and the ALK inhibitor crizotinib further enhances the inhibition.	ibrutinib	31-40	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	17-20
30013190-8	2018	Our study provides strong rationale for clinical trial of ALK-positive neuroblastoma using ibrutinib or the combination of ibrutinib and ALK inhibitors.	ibrutinib	91-100	ALK receptor tyrosine kinase	Homo sapiens	58-61
30013190-8	2018	Our study provides strong rationale for clinical trial of ALK-positive neuroblastoma using ibrutinib or the combination of ibrutinib and ALK inhibitors.	ibrutinib	123-132	ALK receptor tyrosine kinase	Homo sapiens	58-61
30546948-0	2019	Ibrutinib significantly inhibited Bruton"s tyrosine kinase (BTK) phosphorylation,in-vitro proliferation and enhanced overall survival in a preclinical Burkitt lymphoma (BL) model.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	34-58
30209121-9	2018	We also found that BCR pathway inhibition by BTK inhibitors (ibrutinib, acalabrutinib, and BGB-3111) blocks NFATc1 and STAT3 activation, thereby inhibiting IL-10 and PD-L1 expression.	ibrutinib	61-70	Bruton tyrosine kinase	Homo sapiens	45-48
30209121-9	2018	We also found that BCR pathway inhibition by BTK inhibitors (ibrutinib, acalabrutinib, and BGB-3111) blocks NFATc1 and STAT3 activation, thereby inhibiting IL-10 and PD-L1 expression.	ibrutinib	61-70	nuclear factor of activated T cells 1	Homo sapiens	108-114
30209121-9	2018	We also found that BCR pathway inhibition by BTK inhibitors (ibrutinib, acalabrutinib, and BGB-3111) blocks NFATc1 and STAT3 activation, thereby inhibiting IL-10 and PD-L1 expression.	ibrutinib	61-70	signal transducer and activator of transcription 3	Homo sapiens	119-124
30209121-9	2018	We also found that BCR pathway inhibition by BTK inhibitors (ibrutinib, acalabrutinib, and BGB-3111) blocks NFATc1 and STAT3 activation, thereby inhibiting IL-10 and PD-L1 expression.	ibrutinib	61-70	interleukin 10	Homo sapiens	156-161
30209121-9	2018	We also found that BCR pathway inhibition by BTK inhibitors (ibrutinib, acalabrutinib, and BGB-3111) blocks NFATc1 and STAT3 activation, thereby inhibiting IL-10 and PD-L1 expression.	ibrutinib	61-70	CD274 molecule	Homo sapiens	166-171
30305268-1	2018	Activation of MYC, a bona fide client of HSP90, contributes to intrinsic ibrutinib resistance in mantle cell lymphoma.	ibrutinib	73-82	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	14-17
30305268-1	2018	Activation of MYC, a bona fide client of HSP90, contributes to intrinsic ibrutinib resistance in mantle cell lymphoma.	ibrutinib	73-82	heat shock protein 90 alpha family class A member 1	Homo sapiens	41-46
30333099-7	2018	In Townes SCD mice, caspase-1 activity and aggregation of circulating platelets were elevated, which was suppressed by IV injection of an NLRP3 inhibitor and the BTK inhibitor ibrutinib.	ibrutinib	176-185	caspase 1	Mus musculus	20-29
30333099-7	2018	In Townes SCD mice, caspase-1 activity and aggregation of circulating platelets were elevated, which was suppressed by IV injection of an NLRP3 inhibitor and the BTK inhibitor ibrutinib.	ibrutinib	176-185	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	162-165
30416684-2	2018	The BTK-specific inhibitor Ibrutinib blocks BCR signaling and is now approved as effective B-CLL therapy.	ibrutinib	27-36	Bruton tyrosine kinase	Homo sapiens	4-7
30546948-0	2019	Ibrutinib significantly inhibited Bruton"s tyrosine kinase (BTK) phosphorylation,in-vitro proliferation and enhanced overall survival in a preclinical Burkitt lymphoma (BL) model.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	60-63
30546948-3	2019	Ibrutinib, a selective and irreversible BTK inhibitor, has been efficacious in chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenstrom"s macroglobulinemia, and marginal zone lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	40-43
30546948-5	2019	Our data demonstrated that phospho-BTK level was significantly reduced in BL cells treated with ibrutinib (p &lt; 0.001).	ibrutinib	96-105	Bruton tyrosine kinase	Homo sapiens	35-38
28830912-6	2018	We found that this genetic dependency could be elicited with the clinical BTK/ERBB2 kinase inhibitor, ibrutinib.	ibrutinib	102-111	Bruton tyrosine kinase	Homo sapiens	74-77
30089638-11	2018	CD20 mAb-induced ADCP was not inhibited by venetoclax and was less inhibited by acalabrutinib versus ibrutinib and umbralisib versus idelalisib.	ibrutinib	101-110	keratin 20	Homo sapiens	0-4
30093506-0	2018	The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation.	ibrutinib	34-43	Bruton tyrosine kinase	Homo sapiens	4-7
30093506-1	2018	Targeted inhibition of Bruton tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has improved outcomes for patients with hematologic malignancies, including chronic lymphocytic leukemia (CLL).	ibrutinib	84-93	Bruton tyrosine kinase	Homo sapiens	23-45
30093506-1	2018	Targeted inhibition of Bruton tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has improved outcomes for patients with hematologic malignancies, including chronic lymphocytic leukemia (CLL).	ibrutinib	84-93	Bruton tyrosine kinase	Homo sapiens	47-50
30093506-6	2018	Additionally, ARQ 531 inhibits CLL cell survival and suppresses BCR-mediated activation of C481S BTK and PLCgamma2 mutants, which facilitate clinical resistance to ibrutinib.Significance: This study characterizes a rationally designed kinase inhibitor with efficacy in models recapitulating the most common mechanisms of acquired resistance to ibrutinib.	ibrutinib	164-173	phospholipase C gamma 2	Homo sapiens	105-114
30080238-8	2018	Furthermore, we show a close connection between BCR and CD38 signalling, which can be co-targeted with ibrutinib + Dara to induce marked WM cell death, irrespective of acquired resistance to ibrutinib.	ibrutinib	103-112	CD38 antigen	Mus musculus	56-60
30080238-8	2018	Furthermore, we show a close connection between BCR and CD38 signalling, which can be co-targeted with ibrutinib + Dara to induce marked WM cell death, irrespective of acquired resistance to ibrutinib.	ibrutinib	191-200	CD38 antigen	Mus musculus	56-60
28830912-6	2018	We found that this genetic dependency could be elicited with the clinical BTK/ERBB2 kinase inhibitor, ibrutinib.	ibrutinib	102-111	erb-b2 receptor tyrosine kinase 2	Homo sapiens	78-83
28830912-7	2018	In both MYC and ERBB2 amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G1 cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer.	ibrutinib	46-55	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	8-11
28830912-7	2018	In both MYC and ERBB2 amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G1 cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer.	ibrutinib	46-55	erb-b2 receptor tyrosine kinase 2	Homo sapiens	16-21
28830912-7	2018	In both MYC and ERBB2 amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G1 cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer.	ibrutinib	46-55	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	104-108
30190015-4	2018	CXCR4 mutations are identified in approximately 30% of MYD88L265P cases and have been associated with ibrutinib resistance in clinical trials.	ibrutinib	102-111	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
28830912-7	2018	In both MYC and ERBB2 amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G1 cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer.	ibrutinib	46-55	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	105-108
30190023-2	2018	Ibrutinib is a first-generation BTK inhibitor that has shown high activity and durable responses in patients with relapsed/refractory WM.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	32-35
28830912-8	2018	CONCLUSIONS: BTK represents a novel candidate therapeutic target in oesophageal cancer that can be targeted with ibrutinib.	ibrutinib	113-122	Bruton tyrosine kinase	Homo sapiens	13-16
30190023-3	2018	Newer and more selective BTK inhibitors are currently being tested in several clinical trials and are expected to address the toxicity and the acquired resistance observed in patients receiving ibrutinib.	ibrutinib	194-203	Bruton tyrosine kinase	Homo sapiens	25-28
28830912-9	2018	On the basis of this work, a proof-of-concept phase II clinical trial evaluating the efficacy of ibrutinib in patients with MYC and/or ERBB2 amplified advanced oesophageal cancer is currently underway (NCT02884453).	ibrutinib	97-106	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	124-127
28830912-9	2018	On the basis of this work, a proof-of-concept phase II clinical trial evaluating the efficacy of ibrutinib in patients with MYC and/or ERBB2 amplified advanced oesophageal cancer is currently underway (NCT02884453).	ibrutinib	97-106	erb-b2 receptor tyrosine kinase 2	Homo sapiens	135-140
29115892-2	2018	Ibrutinib is an irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and has shown significant efficacy and tolerability, even in heavily treated patients.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	42-66
29115892-2	2018	Ibrutinib is an irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and has shown significant efficacy and tolerability, even in heavily treated patients.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	68-71
30065099-3	2018	Because the PI3K/AKT/mTOR pathway is one of the major downstream pathways of EGFR, we hypothesized that ibrutinib"s activity might be enhanced by combination therapy with auranofin in NSCLC cells.	ibrutinib	104-113	AKT serine/threonine kinase 1	Homo sapiens	17-20
30065099-3	2018	Because the PI3K/AKT/mTOR pathway is one of the major downstream pathways of EGFR, we hypothesized that ibrutinib"s activity might be enhanced by combination therapy with auranofin in NSCLC cells.	ibrutinib	104-113	mechanistic target of rapamycin kinase	Homo sapiens	21-25
30065099-0	2018	Auranofin Enhances Ibrutinib"s Anticancer Activity in EGFR-Mutant Lung Adenocarcinoma.	ibrutinib	19-28	epidermal growth factor receptor	Homo sapiens	54-58
30065099-1	2018	We previously found that ibrutinib has anticancer activity in EGFR-mutant non-small cell lung cancer (NSCLC).	ibrutinib	25-34	epidermal growth factor receptor	Homo sapiens	62-66
30065099-3	2018	Because the PI3K/AKT/mTOR pathway is one of the major downstream pathways of EGFR, we hypothesized that ibrutinib"s activity might be enhanced by combination therapy with auranofin in NSCLC cells.	ibrutinib	104-113	epidermal growth factor receptor	Homo sapiens	77-81
30065099-4	2018	To this end, we examined ibrutinib"s dose responses in EGFR-mutant H1975, PC9, and H1650 cells and in EGFR wild-type Calu3 and H460 cells in the presence or absence of auranofin.	ibrutinib	25-34	epidermal growth factor receptor	Homo sapiens	55-59
30065099-4	2018	To this end, we examined ibrutinib"s dose responses in EGFR-mutant H1975, PC9, and H1650 cells and in EGFR wild-type Calu3 and H460 cells in the presence or absence of auranofin.	ibrutinib	25-34	proprotein convertase subtilisin/kexin type 9	Homo sapiens	74-77
30065099-5	2018	Although low concentrations of auranofin alone demonstrated mild anticancer activities, its presence dramatically enhanced ibrutinib"s activity in H1975, PC9, and H1650 cells (IC50 value reduced 10- to 100-fold), but had only mild effect on Calu3 and H460 cells, demonstrating that ibrutinib"s anti-EGFR activity is enhanced when it is combined with auranofin.	ibrutinib	123-132	proprotein convertase subtilisin/kexin type 9	Homo sapiens	154-157
30065099-6	2018	A mechanistic analysis revealed that ibrutinib alone induced dramatic inhibition of the MEK/ERK pathway in both H1975 and H1650 cells, whereas auranofin alone inhibited the AKT/mTOR pathway.	ibrutinib	37-46	mitogen-activated protein kinase kinase 7	Homo sapiens	88-91
30065099-6	2018	A mechanistic analysis revealed that ibrutinib alone induced dramatic inhibition of the MEK/ERK pathway in both H1975 and H1650 cells, whereas auranofin alone inhibited the AKT/mTOR pathway.	ibrutinib	37-46	mitogen-activated protein kinase 1	Homo sapiens	92-95
30065099-7	2018	The combination of ibrutinib and auranofin led to a dramatically enhanced inhibition of the expression or phosphorylation of multiple key nodes in the AKT/mTOR and MEK/ERK pathways in both cell lines.	ibrutinib	19-28	AKT serine/threonine kinase 1	Homo sapiens	151-154
30065099-7	2018	The combination of ibrutinib and auranofin led to a dramatically enhanced inhibition of the expression or phosphorylation of multiple key nodes in the AKT/mTOR and MEK/ERK pathways in both cell lines.	ibrutinib	19-28	mechanistic target of rapamycin kinase	Homo sapiens	155-159
30065099-7	2018	The combination of ibrutinib and auranofin led to a dramatically enhanced inhibition of the expression or phosphorylation of multiple key nodes in the AKT/mTOR and MEK/ERK pathways in both cell lines.	ibrutinib	19-28	mitogen-activated protein kinase kinase 7	Homo sapiens	164-167
30065099-7	2018	The combination of ibrutinib and auranofin led to a dramatically enhanced inhibition of the expression or phosphorylation of multiple key nodes in the AKT/mTOR and MEK/ERK pathways in both cell lines.	ibrutinib	19-28	mitogen-activated protein kinase 1	Homo sapiens	168-171
30065099-9	2018	Our results demonstrate the feasibility of improving ibrutinib"s anti-EGFR activity for NSCLC using combination therapy with auranofin.	ibrutinib	53-62	epidermal growth factor receptor	Homo sapiens	70-74
29895969-8	2018	In accordance with functional enrichment analyses in gene expression profiling, CLL cells with depletion or inhibition of MELK exhibited impaired cell proliferation, enhanced fast-onset apoptosis, induced G2/M arrest, attenuated cell chemotaxis and promoted sensitivity to fludarabine and ibrutinib.	ibrutinib	289-298	maternal embryonic leucine zipper kinase	Homo sapiens	122-126
30231870-2	2018	Ibrutinib inhibits Bruton"s tyrosine kinase (BTK), a kinase involved in B cell receptor signaling.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	19-43
30344948-0	2018	Functional characterization of phospholipase C-gamma2 mutant protein causing both somatic ibrutinib resistance and a germline monogenic autoinflammatory disorder.	ibrutinib	90-99	phospholipase C gamma 2	Homo sapiens	31-53
30011241-1	2018	Bruton"s tyrosine kinase (BTK) is a clinically validated target for B-cell leukemias and lymphomas with FDA-approved small-molecule inhibitors ibrutinib and acalabrutinib.	ibrutinib	143-152	Bruton tyrosine kinase	Homo sapiens	0-24
30011241-1	2018	Bruton"s tyrosine kinase (BTK) is a clinically validated target for B-cell leukemias and lymphomas with FDA-approved small-molecule inhibitors ibrutinib and acalabrutinib.	ibrutinib	143-152	Bruton tyrosine kinase	Homo sapiens	26-29
30044692-2	2018	MYD88 mutations ( MYD88MUT) and CXCR4 mutations ( CXCR4MUT) affect ibrutinib response.	ibrutinib	67-76	MYD88 innate immune signal transduction adaptor	Homo sapiens	0-5
30044692-2	2018	MYD88 mutations ( MYD88MUT) and CXCR4 mutations ( CXCR4MUT) affect ibrutinib response.	ibrutinib	67-76	C-X-C motif chemokine receptor 4	Homo sapiens	32-37
30012921-1	2018	Ibrutinib (IBR) covalently binds to the active site of Bruton"s tyrosine kinase (BTK) and is used for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	55-79
30012921-1	2018	Ibrutinib (IBR) covalently binds to the active site of Bruton"s tyrosine kinase (BTK) and is used for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	81-84
30231870-2	2018	Ibrutinib inhibits Bruton"s tyrosine kinase (BTK), a kinase involved in B cell receptor signaling.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	45-48
30231870-11	2018	Ibrutinib regulated TLR4 signaling to alter LPS-induced proinflammatory cytokine levels.	ibrutinib	0-9	toll-like receptor 4	Mus musculus	20-24
30231870-12	2018	In addition, ibrutinib significantly decreased LPS-induced increases in p-AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways.	ibrutinib	13-22	thymoma viral proto-oncogene 1	Mus musculus	74-77
30231870-12	2018	In addition, ibrutinib significantly decreased LPS-induced increases in p-AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways.	ibrutinib	13-22	signal transducer and activator of transcription 3	Mus musculus	84-89
30231870-12	2018	In addition, ibrutinib significantly decreased LPS-induced increases in p-AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways.	ibrutinib	13-22	thymoma viral proto-oncogene 1	Mus musculus	189-192
30231870-12	2018	In addition, ibrutinib significantly decreased LPS-induced increases in p-AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways.	ibrutinib	13-22	signal transducer and activator of transcription 3	Mus musculus	193-198
30231870-12	2018	In addition, ibrutinib significantly decreased LPS-induced increases in p-AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways.	ibrutinib	114-123	thymoma viral proto-oncogene 1	Mus musculus	74-77
30231870-12	2018	In addition, ibrutinib significantly decreased LPS-induced increases in p-AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways.	ibrutinib	114-123	signal transducer and activator of transcription 3	Mus musculus	84-89
30231870-12	2018	In addition, ibrutinib significantly decreased LPS-induced increases in p-AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways.	ibrutinib	114-123	thymoma viral proto-oncogene 1	Mus musculus	189-192
30231870-12	2018	In addition, ibrutinib significantly decreased LPS-induced increases in p-AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways.	ibrutinib	114-123	signal transducer and activator of transcription 3	Mus musculus	193-198
30231870-13	2018	Interestingly, ibrutinib also reduced LPS-induced BV2 microglial cell migration by inhibiting AKT signaling.	ibrutinib	15-24	thymoma viral proto-oncogene 1	Mus musculus	94-97
30231870-14	2018	Moreover, ibrutinib-injected wild-type mice exhibited significantly reduced microglial/astrocyte activation and COX-2 and IL-1beta proinflammatory cytokine levels.	ibrutinib	10-19	cytochrome c oxidase II, mitochondrial	Mus musculus	112-117
30231870-14	2018	Moreover, ibrutinib-injected wild-type mice exhibited significantly reduced microglial/astrocyte activation and COX-2 and IL-1beta proinflammatory cytokine levels.	ibrutinib	10-19	interleukin 1 beta	Mus musculus	122-130
30012673-7	2018	Inhibition of BMX with ibrutinib (developed as an inhibitor of the related Tec kinase BTK) or another BMX inhibitor BMX-IN-1 markedly enhanced the response to castration in a prostate cancer xenograft model.	ibrutinib	23-32	BMX non-receptor tyrosine kinase	Homo sapiens	14-17
30012673-7	2018	Inhibition of BMX with ibrutinib (developed as an inhibitor of the related Tec kinase BTK) or another BMX inhibitor BMX-IN-1 markedly enhanced the response to castration in a prostate cancer xenograft model.	ibrutinib	23-32	Bruton tyrosine kinase	Homo sapiens	86-89
29978459-2	2018	Ibrutinib and idelalisib, which inhibit Bruton Tyrosine kinase (BTK) and phosphoinositol-3 (PI3) kinase-delta respectively, have become important treatment options for the disease and demonstrate the potential of targeting components of the B-cell receptor-signalling pathway.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	40-62
30018078-0	2018	Noncovalent inhibition of C481S Bruton tyrosine kinase by GDC-0853: a new treatment strategy for ibrutinib-resistant CLL.	ibrutinib	97-106	Bruton tyrosine kinase	Homo sapiens	32-54
30018078-1	2018	The clinical success of ibrutinib validates Bruton tyrosine kinase (BTK) inhibition as an effective strategy for treating hematologic malignancies, including chronic lymphocytic leukemia (CLL).	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	44-66
30018078-1	2018	The clinical success of ibrutinib validates Bruton tyrosine kinase (BTK) inhibition as an effective strategy for treating hematologic malignancies, including chronic lymphocytic leukemia (CLL).	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	68-71
30018078-2	2018	Despite ibrutinib"s ability to produce durable remissions in patients, acquired resistance can develop, mostly commonly by mutation of C481 of BTK in the ibrutinib binding site.	ibrutinib	8-17	Bruton tyrosine kinase	Homo sapiens	143-146
30018078-2	2018	Despite ibrutinib"s ability to produce durable remissions in patients, acquired resistance can develop, mostly commonly by mutation of C481 of BTK in the ibrutinib binding site.	ibrutinib	154-163	Bruton tyrosine kinase	Homo sapiens	143-146
30018078-6	2018	We found that GDC-0853 also inhibits the most commonly reported ibrutinib-resistant BTK mutant (C481S) both in a biochemical enzyme activity assay and in a stably transfected 293T cell line and maintains cytotoxicity against patient CLL cells harboring C481S BTK mutations.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	84-87
30018078-6	2018	We found that GDC-0853 also inhibits the most commonly reported ibrutinib-resistant BTK mutant (C481S) both in a biochemical enzyme activity assay and in a stably transfected 293T cell line and maintains cytotoxicity against patient CLL cells harboring C481S BTK mutations.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	259-262
30018078-8	2018	Our results using GDC-0853 indicate that noncovalent, selective BTK inhibition may be effective in CLL either as monotherapy or in combination with therapeutic antibodies, especially among the emerging population of patients with acquired resistance to ibrutinib therapy.	ibrutinib	253-262	Bruton tyrosine kinase	Homo sapiens	64-67
29995658-1	2018	: Ibrutinib is the first drug of a new family of Bruton"s tyrosine kinases (Btk)-inhibiting agents, which have proved to be useful for the treatment of several B-cell lymphoid malignancies.	ibrutinib	2-11	Bruton tyrosine kinase	Homo sapiens	49-74
29995658-1	2018	: Ibrutinib is the first drug of a new family of Bruton"s tyrosine kinases (Btk)-inhibiting agents, which have proved to be useful for the treatment of several B-cell lymphoid malignancies.	ibrutinib	2-11	Bruton tyrosine kinase	Homo sapiens	76-79
29995658-3	2018	Although Btk plays an important role in platelet signalling, increased bleeding tendency in patients on ibrutinib is more complex than Btk inhibition alone and is because of several antiplatelet mechanisms, namely inhibition of Btk and Tec kinases, which play a key role in platelet activation downstream of the collagen GPVI and Glycoprotein Ib.	ibrutinib	104-113	Bruton tyrosine kinase	Homo sapiens	9-12
29995658-3	2018	Although Btk plays an important role in platelet signalling, increased bleeding tendency in patients on ibrutinib is more complex than Btk inhibition alone and is because of several antiplatelet mechanisms, namely inhibition of Btk and Tec kinases, which play a key role in platelet activation downstream of the collagen GPVI and Glycoprotein Ib.	ibrutinib	104-113	Bruton tyrosine kinase	Homo sapiens	135-138
29995658-3	2018	Although Btk plays an important role in platelet signalling, increased bleeding tendency in patients on ibrutinib is more complex than Btk inhibition alone and is because of several antiplatelet mechanisms, namely inhibition of Btk and Tec kinases, which play a key role in platelet activation downstream of the collagen GPVI and Glycoprotein Ib.	ibrutinib	104-113	Bruton tyrosine kinase	Homo sapiens	135-138
30122225-2	2018	Small molecule covalent irreversible BTK inhibitor targeting Cys481 within the ATP-binding pocket, for example ibrutinib, has been applied in the treatment of B-cell malignancies.	ibrutinib	111-120	Bruton tyrosine kinase	Homo sapiens	37-40
30237801-3	2018	Here, using primary B cells from distinct mouse models and the pharmacological inhibitors ibrutinib and acalabrutinib, we report distinct roles for Btk in antigen-triggered immune synapse (IS) formation.	ibrutinib	90-99	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	148-151
29978459-2	2018	Ibrutinib and idelalisib, which inhibit Bruton Tyrosine kinase (BTK) and phosphoinositol-3 (PI3) kinase-delta respectively, have become important treatment options for the disease and demonstrate the potential of targeting components of the B-cell receptor-signalling pathway.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	64-67
30052472-2	2018	Bruton tyrosine kinase (BTK) is a key receptor in B-cell tumorigenesis, and the benefits of the first BTK inhibitor, ibrutinib, are becoming clear in MCL.	ibrutinib	117-126	Bruton tyrosine kinase	Homo sapiens	0-22
29995658-3	2018	Although Btk plays an important role in platelet signalling, increased bleeding tendency in patients on ibrutinib is more complex than Btk inhibition alone and is because of several antiplatelet mechanisms, namely inhibition of Btk and Tec kinases, which play a key role in platelet activation downstream of the collagen GPVI and Glycoprotein Ib.	ibrutinib	104-113	glycoprotein VI platelet	Homo sapiens	321-325
30052472-2	2018	Bruton tyrosine kinase (BTK) is a key receptor in B-cell tumorigenesis, and the benefits of the first BTK inhibitor, ibrutinib, are becoming clear in MCL.	ibrutinib	117-126	Bruton tyrosine kinase	Homo sapiens	24-27
30052472-2	2018	Bruton tyrosine kinase (BTK) is a key receptor in B-cell tumorigenesis, and the benefits of the first BTK inhibitor, ibrutinib, are becoming clear in MCL.	ibrutinib	117-126	Bruton tyrosine kinase	Homo sapiens	102-105
30029202-1	2018	Ibrutinib is an orally administered first-in-class irreversible Bruton"s tyrosine kinase (BTK) covalent inhibitor for the treatment of patients with B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	64-88
29295653-0	2018	Improvement of fatigue, physical functioning, and well-being among patients with severe impairment at baseline receiving ibrutinib in combination with bendamustine and rituximab for relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma in the HELIOS study.	ibrutinib	121-130	IKAROS family zinc finger 2	Homo sapiens	254-260
30149317-1	2018	There is the first evidence of changes in the kinetics of B cell antigen receptor (BCR) internalisation of neoplastic cells in chronic lymphocytic leukemia (CLL) after the short-term and long-term administration of ibrutinib.	ibrutinib	215-224	BCR activator of RhoGEF and GTPase	Homo sapiens	58-81
30149317-1	2018	There is the first evidence of changes in the kinetics of B cell antigen receptor (BCR) internalisation of neoplastic cells in chronic lymphocytic leukemia (CLL) after the short-term and long-term administration of ibrutinib.	ibrutinib	215-224	BCR activator of RhoGEF and GTPase	Homo sapiens	83-86
30149317-8	2018	The long-term administration of ibrutinib was associated with the increased numbers of CD4+ bearing HLA-DR (P = 0.006) and elevation of HLA-DR expression on all monocyte subsets (P &lt;= 0.004).	ibrutinib	32-41	CD4 molecule	Homo sapiens	87-90
29869556-1	2018	Waldenstrom macroglobulinemia (WM), an incurable B-cell malignancy, is sensitive to Bruton tyrosine kinase (BTK) inhibition with ibrutinib, a first-generation BTK inhibitor.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	84-106
29869556-1	2018	Waldenstrom macroglobulinemia (WM), an incurable B-cell malignancy, is sensitive to Bruton tyrosine kinase (BTK) inhibition with ibrutinib, a first-generation BTK inhibitor.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	108-111
29869556-1	2018	Waldenstrom macroglobulinemia (WM), an incurable B-cell malignancy, is sensitive to Bruton tyrosine kinase (BTK) inhibition with ibrutinib, a first-generation BTK inhibitor.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	159-162
29869556-2	2018	Off-target effects of ibrutinib against TEC- and EGFR-family kinases are implicated in some adverse events.	ibrutinib	22-31	tec protein tyrosine kinase	Homo sapiens	40-44
29869556-3	2018	Patients with CXCR4WHIM and MYD88L265P mutations or who are MYD88WT have less sensitivity to ibrutinib than those with MYD88L265P and CXCR4WT disease.	ibrutinib	93-102	C-X-C motif chemokine receptor 4	Homo sapiens	14-19
30029202-1	2018	Ibrutinib is an orally administered first-in-class irreversible Bruton"s tyrosine kinase (BTK) covalent inhibitor for the treatment of patients with B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	90-93
30115641-0	2018	Activation of MYC, a bona fide client of HSP90, contributes to intrinsic ibrutinib resistance in mantle cell lymphoma.	ibrutinib	73-82	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	14-17
30115641-0	2018	Activation of MYC, a bona fide client of HSP90, contributes to intrinsic ibrutinib resistance in mantle cell lymphoma.	ibrutinib	73-82	heat shock protein 90 alpha family class A member 1	Homo sapiens	41-46
30115641-1	2018	The BTK inhibitor ibrutinib has demonstrated a remarkable therapeutic effect in mantle cell lymphoma (MCL).	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
30115641-4	2018	We found that MYC gene signature was suppressed by ibrutinib in sensitive but not resistant cell lines.	ibrutinib	51-60	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	14-17
30115641-6	2018	Further, MYC knockdown with RNA interference inhibited cell growth in ibrutinib-sensitive as well as ibrutinib-resistant cells.	ibrutinib	70-79	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	9-12
30115641-6	2018	Further, MYC knockdown with RNA interference inhibited cell growth in ibrutinib-sensitive as well as ibrutinib-resistant cells.	ibrutinib	101-110	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	9-12
30115641-14	2018	In conclusion, MYC activity underlies intrinsic resistance to ibrutinib in MCL.	ibrutinib	62-71	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	15-18
30115641-15	2018	As a client protein of HSP90, MYC can be inhibited via PU-H71 to overcome primary ibrutinib resistance.	ibrutinib	82-91	heat shock protein 90 alpha family class A member 1	Homo sapiens	23-28
30115641-15	2018	As a client protein of HSP90, MYC can be inhibited via PU-H71 to overcome primary ibrutinib resistance.	ibrutinib	82-91	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	30-33
29526963-2	2018	We herein report the first patient with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL)-associated PNP successfully treated with the Bruton"s tyrosine kinase inhibitor ibrutinib and rituximab.	ibrutinib	195-204	solute carrier family 35 member B2	Homo sapiens	104-113
30186643-0	2018	Ibrutinib Treatment through Nasogastric Tube in a Comatose Patient with Central Nervous System Localization of Mantle Cell Lymphoma.	ibrutinib	0-9	tubulin epsilon 1	Homo sapiens	40-44
30186643-6	2018	The patient then received ibrutinib via a nasogastric tube at a dose of 560 mg daily.	ibrutinib	26-35	tubulin epsilon 1	Homo sapiens	54-58
30186643-9	2018	We believe that the administration of ibrutinib through the nasogastric tube was a determinant factor in this patient"s remission and survival.	ibrutinib	38-47	tubulin epsilon 1	Homo sapiens	72-76
29526963-2	2018	We herein report the first patient with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL)-associated PNP successfully treated with the Bruton"s tyrosine kinase inhibitor ibrutinib and rituximab.	ibrutinib	195-204	Bruton tyrosine kinase	Homo sapiens	160-184
29526963-3	2018	Although his PNP lesions did not improve with ibrutinib monotherapy, the combination of ibrutinib and rituximab was effective against B-CLL/SLL-associated PNP.	ibrutinib	88-97	solute carrier family 35 member B2	Homo sapiens	134-143
29526963-4	2018	This case suggests that ibrutinib plus rituximab may be a potent therapeutic option for B-CLL/SLL-associated PNP that is hard to control with ibrutinib alone.	ibrutinib	24-33	solute carrier family 35 member B2	Homo sapiens	94-97
29743179-0	2018	A CD19/CD3 bispecific antibody for effective immunotherapy of chronic lymphocytic leukemia in the ibrutinib era.	ibrutinib	98-107	CD19 molecule	Homo sapiens	2-6
29509845-1	2018	Background: Ibrutinib is a Bruton tyrosine kinase inhibitor that is used for the treatment of lymphoid cancers, including chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, and mantle cell lymphoma.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	27-49
29743179-10	2018	We next explored the activity of CD19/CD3-scFv-Fc in the context of ibrutinib treatment and ibrutinib resistance.	ibrutinib	68-77	CD19 molecule	Homo sapiens	33-37
29743179-0	2018	A CD19/CD3 bispecific antibody for effective immunotherapy of chronic lymphocytic leukemia in the ibrutinib era.	ibrutinib	98-107	CD3 antigen, epsilon polypeptide	Mus musculus	7-10
29743179-11	2018	CD19/CD3-scFv-Fc induced more rapid killing of CLL cells from ibrutinib-treated patients than those from treatment-naive patients.	ibrutinib	62-71	CD19 molecule	Homo sapiens	0-4
29882017-8	2018	RESULTS: AUC48h and AUClast of ibrutinib plus omeprazole versus ibrutinib alone showed a modest decrease (GMR [90% CI] 98.3% [83.1-116.3] and 92.5% [77.8-109.9], respectively); Cmax decreased by 62.5% (GMR [90% CI] 37.5% [26.4-53.4]), with delayed tmax (1-2 h) and terminal half-life unaffected.	ibrutinib	31-40	colony stimulating factor 2 receptor subunit alpha	Homo sapiens	106-109
29743179-11	2018	CD19/CD3-scFv-Fc induced more rapid killing of CLL cells from ibrutinib-treated patients than those from treatment-naive patients.	ibrutinib	62-71	CD3 antigen, epsilon polypeptide	Mus musculus	5-8
29743179-11	2018	CD19/CD3-scFv-Fc induced more rapid killing of CLL cells from ibrutinib-treated patients than those from treatment-naive patients.	ibrutinib	62-71	immunglobulin heavy chain variable region	Homo sapiens	9-13
29743179-12	2018	CD19/CD3-scFv-Fc also demonstrated potent activity against CLL cells from patients with acquired ibrutinib-resistance harboring BTK and/or PLCG2 mutations in vitro and in vivo using patient-derived xenograft models.	ibrutinib	97-106	CD19 molecule	Homo sapiens	0-4
29743179-12	2018	CD19/CD3-scFv-Fc also demonstrated potent activity against CLL cells from patients with acquired ibrutinib-resistance harboring BTK and/or PLCG2 mutations in vitro and in vivo using patient-derived xenograft models.	ibrutinib	97-106	CD3 antigen, epsilon polypeptide	Mus musculus	5-8
29743179-12	2018	CD19/CD3-scFv-Fc also demonstrated potent activity against CLL cells from patients with acquired ibrutinib-resistance harboring BTK and/or PLCG2 mutations in vitro and in vivo using patient-derived xenograft models.	ibrutinib	97-106	immunglobulin heavy chain variable region	Homo sapiens	9-13
29743179-12	2018	CD19/CD3-scFv-Fc also demonstrated potent activity against CLL cells from patients with acquired ibrutinib-resistance harboring BTK and/or PLCG2 mutations in vitro and in vivo using patient-derived xenograft models.	ibrutinib	97-106	Bruton tyrosine kinase	Homo sapiens	128-131
29743179-12	2018	CD19/CD3-scFv-Fc also demonstrated potent activity against CLL cells from patients with acquired ibrutinib-resistance harboring BTK and/or PLCG2 mutations in vitro and in vivo using patient-derived xenograft models.	ibrutinib	97-106	phospholipase C gamma 2	Homo sapiens	139-144
29280186-6	2018	A baseline platelet count &lt;=100 K/microL and presence of tumor CXCR4 mutations were independently associated with 4-fold increased odds of ibrutinib discontinuation.	ibrutinib	142-151	C-X-C motif chemokine receptor 4	Homo sapiens	66-71
29882017-8	2018	RESULTS: AUC48h and AUClast of ibrutinib plus omeprazole versus ibrutinib alone showed a modest decrease (GMR [90% CI] 98.3% [83.1-116.3] and 92.5% [77.8-109.9], respectively); Cmax decreased by 62.5% (GMR [90% CI] 37.5% [26.4-53.4]), with delayed tmax (1-2 h) and terminal half-life unaffected.	ibrutinib	31-40	colony stimulating factor 2 receptor subunit alpha	Homo sapiens	202-205
29882017-8	2018	RESULTS: AUC48h and AUClast of ibrutinib plus omeprazole versus ibrutinib alone showed a modest decrease (GMR [90% CI] 98.3% [83.1-116.3] and 92.5% [77.8-109.9], respectively); Cmax decreased by 62.5% (GMR [90% CI] 37.5% [26.4-53.4]), with delayed tmax (1-2 h) and terminal half-life unaffected.	ibrutinib	64-73	colony stimulating factor 2 receptor subunit alpha	Homo sapiens	106-109
29164976-4	2018	Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion.	ibrutinib	0-9	Fc epsilon receptor II	Homo sapiens	84-88
29164976-4	2018	Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion.	ibrutinib	0-9	CD27 molecule	Homo sapiens	90-94
29164976-4	2018	Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion.	ibrutinib	0-9	CD53 molecule	Homo sapiens	96-100
29164976-4	2018	Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion.	ibrutinib	0-9	CD58 molecule	Homo sapiens	102-106
29164976-4	2018	Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion.	ibrutinib	0-9	transferrin receptor	Homo sapiens	108-112
29164976-4	2018	Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion.	ibrutinib	0-9	CD80 molecule	Homo sapiens	114-118
29164976-4	2018	Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion.	ibrutinib	0-9	CD84 molecule	Homo sapiens	120-124
29164976-4	2018	Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion.	ibrutinib	0-9	adhesion G protein-coupled receptor E5	Homo sapiens	126-130
29164976-4	2018	Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion.	ibrutinib	0-9	interleukin 6 receptor	Homo sapiens	132-137
29164976-4	2018	Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion.	ibrutinib	0-9	signaling lymphocytic activation molecule family member 1	Homo sapiens	139-144
29925955-5	2018	In a clinical trial, the BTK inhibitor ibrutinib produced responses in 37% of cases of ABC1.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	25-28
29925955-8	2018	We discovered a new mode of oncogenic BCR signalling in ibrutinib-responsive cell lines and biopsies, coordinated by a multiprotein supercomplex formed by MYD88, TLR9 and the BCR (hereafter termed the My-T-BCR supercomplex).	ibrutinib	56-65	MYD88 innate immune signal transduction adaptor	Homo sapiens	155-160
29925955-5	2018	In a clinical trial, the BTK inhibitor ibrutinib produced responses in 37% of cases of ABC1.	ibrutinib	39-48	ATP binding cassette subfamily A member 1	Homo sapiens	87-91
29925955-8	2018	We discovered a new mode of oncogenic BCR signalling in ibrutinib-responsive cell lines and biopsies, coordinated by a multiprotein supercomplex formed by MYD88, TLR9 and the BCR (hereafter termed the My-T-BCR supercomplex).	ibrutinib	56-65	toll like receptor 9	Homo sapiens	162-166
30030853-3	2018	In clinical studies, BTK inhibitors (ibrutinib, acalabrutinib, tirabrutinib, zanubrutinib) have been associated with increased bleeding risk, which may result from inhibition of BTK alone or of both BTK and TEC, although the role of TEC in bleeding risk remains unclear.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	21-24
30030853-3	2018	In clinical studies, BTK inhibitors (ibrutinib, acalabrutinib, tirabrutinib, zanubrutinib) have been associated with increased bleeding risk, which may result from inhibition of BTK alone or of both BTK and TEC, although the role of TEC in bleeding risk remains unclear.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	178-181
30030853-3	2018	In clinical studies, BTK inhibitors (ibrutinib, acalabrutinib, tirabrutinib, zanubrutinib) have been associated with increased bleeding risk, which may result from inhibition of BTK alone or of both BTK and TEC, although the role of TEC in bleeding risk remains unclear.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	178-181
30030853-3	2018	In clinical studies, BTK inhibitors (ibrutinib, acalabrutinib, tirabrutinib, zanubrutinib) have been associated with increased bleeding risk, which may result from inhibition of BTK alone or of both BTK and TEC, although the role of TEC in bleeding risk remains unclear.	ibrutinib	37-46	tec protein tyrosine kinase	Homo sapiens	207-210
30030853-3	2018	In clinical studies, BTK inhibitors (ibrutinib, acalabrutinib, tirabrutinib, zanubrutinib) have been associated with increased bleeding risk, which may result from inhibition of BTK alone or of both BTK and TEC, although the role of TEC in bleeding risk remains unclear.	ibrutinib	37-46	tec protein tyrosine kinase	Homo sapiens	233-236
30030853-8	2018	At clinically relevant plasma concentration, ibrutinib, acalabrutinib, and tirabrutinib inhibited collagen-induced platelet aggregation to a similar extent, despite differing in vitro IC50 s. CONCLUSIONS: Our results suggest BTK inhibition is the primary driver for inhibition of platelet aggregation.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	225-228
30123049-6	2018	The secretion of cytokines (IL-6, IL-2 and IFN-gamma) was suppressed in response to ibrutinib.	ibrutinib	84-93	interleukin 6	Homo sapiens	28-32
30123049-6	2018	The secretion of cytokines (IL-6, IL-2 and IFN-gamma) was suppressed in response to ibrutinib.	ibrutinib	84-93	interleukin 2	Homo sapiens	34-38
30123049-6	2018	The secretion of cytokines (IL-6, IL-2 and IFN-gamma) was suppressed in response to ibrutinib.	ibrutinib	84-93	interferon gamma	Homo sapiens	43-52
29851337-0	2018	Targeting the C481S Ibrutinib-Resistance Mutation in Bruton"s Tyrosine Kinase Using PROTAC-Mediated Degradation.	ibrutinib	20-29	Bruton tyrosine kinase	Homo sapiens	53-77
29851337-1	2018	Inhibition of Bruton"s tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has emerged as a transformative treatment option for patients with chronic lymphocytic leukemia (CLL) and other B-cell malignancies, yet &gt;80% of CLL patients develop resistance due to a cysteine to serine mutation at the site covalently bound by ibrutinib (C481S).	ibrutinib	77-86	Bruton tyrosine kinase	Homo sapiens	14-38
29851337-1	2018	Inhibition of Bruton"s tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has emerged as a transformative treatment option for patients with chronic lymphocytic leukemia (CLL) and other B-cell malignancies, yet &gt;80% of CLL patients develop resistance due to a cysteine to serine mutation at the site covalently bound by ibrutinib (C481S).	ibrutinib	77-86	Bruton tyrosine kinase	Homo sapiens	40-43
29851337-1	2018	Inhibition of Bruton"s tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has emerged as a transformative treatment option for patients with chronic lymphocytic leukemia (CLL) and other B-cell malignancies, yet &gt;80% of CLL patients develop resistance due to a cysteine to serine mutation at the site covalently bound by ibrutinib (C481S).	ibrutinib	336-345	Bruton tyrosine kinase	Homo sapiens	14-38
29851337-1	2018	Inhibition of Bruton"s tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has emerged as a transformative treatment option for patients with chronic lymphocytic leukemia (CLL) and other B-cell malignancies, yet &gt;80% of CLL patients develop resistance due to a cysteine to serine mutation at the site covalently bound by ibrutinib (C481S).	ibrutinib	336-345	Bruton tyrosine kinase	Homo sapiens	40-43
29875397-0	2018	PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies.	ibrutinib	80-89	Bruton tyrosine kinase	Homo sapiens	15-18
29741794-5	2018	Remarkable achievements have been made in the pursuit of selective BTK inhibitors, represented by the success of the irreversible BTK inhibitors, ibrutinib and acalabrutinib.	ibrutinib	146-155	Bruton tyrosine kinase	Homo sapiens	67-70
29516781-3	2018	The Btk inhibitor ibrutinib (also known as PCI-32765) was administered intranasally to mice starting 72 h after lethal infection with IAV.	ibrutinib	18-27	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	4-7
29875397-0	2018	PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies.	ibrutinib	80-89	Bruton tyrosine kinase	Homo sapiens	62-65
29855199-6	2018	EXPERT OPINION: While the excellent response rates and favorable toxicity profile of the BTK inhibitor ibrutinib in certain NHL subtypes have propelled it to consideration as frontline therapy in selected populations, additional data and clinical studies are needed before other agents targeting BCR signaling influence clinical practice similarly.	ibrutinib	103-112	Bruton tyrosine kinase	Homo sapiens	89-92
29983879-10	2018	Interestingly, PTC596, reported to target cancer stem cells, decreased MCL-1 expression levels and antagonized ibrutinib-induced increase in MCL-1 expression, leading to synergistic apoptosis induction in MCL cells.	ibrutinib	111-120	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	141-146
29777941-0	2018	Characterization of the binding of a novel antitumor drug ibrutinib with human serum albumin: Insights from spectroscopic, calorimetric and docking studies.	ibrutinib	58-67	albumin	Homo sapiens	79-92
29907126-5	2018	Targeted agents such as ibrutinib, an inhibitor of Bruton"s tyrosine kinase, which has been approved only in the relapsed setting, can be used to treat patients with relapsed or refractory mantle cell lymphoma.	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	51-75
29559479-2	2018	GPIb and GPVI signal through Bruton tyrosine kinase (Btk), which can be blocked irreversibly by oral application of ibrutinib, an established therapy for chronic lymphocytic leukemia (CLL) with long-term safety.	ibrutinib	116-125	glycoprotein VI platelet	Homo sapiens	9-13
29559479-2	2018	GPIb and GPVI signal through Bruton tyrosine kinase (Btk), which can be blocked irreversibly by oral application of ibrutinib, an established therapy for chronic lymphocytic leukemia (CLL) with long-term safety.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	29-51
29559479-2	2018	GPIb and GPVI signal through Bruton tyrosine kinase (Btk), which can be blocked irreversibly by oral application of ibrutinib, an established therapy for chronic lymphocytic leukemia (CLL) with long-term safety.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	53-56
29559479-3	2018	We found that ibrutinib and the novel Btk inhibitors acalabrutinib and ONO/GS-4059 block GPVI-dependent static platelet aggregation in blood exposed to human plaque homogenate and collagen but not to ADP or arachidonic acid.	ibrutinib	14-23	glycoprotein VI platelet	Homo sapiens	89-93
29899297-2	2018	We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor.	ibrutinib	92-101	Bruton tyrosine kinase	Homo sapiens	105-129
29899297-2	2018	We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor.	ibrutinib	92-101	Bruton tyrosine kinase	Homo sapiens	131-134
29899297-9	2018	In addition, an IgH-IRF8 translocation was detected (which brings the IRF8 transcription factor under control of the immunoglobulin heavy chain locus), representing a third plausible mechanism contributing to ibrutinib resistance.	ibrutinib	209-218	immunoglobulin heavy locus	Homo sapiens	16-19
29899297-9	2018	In addition, an IgH-IRF8 translocation was detected (which brings the IRF8 transcription factor under control of the immunoglobulin heavy chain locus), representing a third plausible mechanism contributing to ibrutinib resistance.	ibrutinib	209-218	interferon regulatory factor 8	Homo sapiens	20-24
29899297-9	2018	In addition, an IgH-IRF8 translocation was detected (which brings the IRF8 transcription factor under control of the immunoglobulin heavy chain locus), representing a third plausible mechanism contributing to ibrutinib resistance.	ibrutinib	209-218	interferon regulatory factor 8	Homo sapiens	70-74
29891001-1	2018	BACKGROUND: Ibrutinib is an oral irreversible inhibitor of Bruton"s tyrosine kinase, indicated for the treatment of chronic lymphocytic leukaemia.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	59-83
29856777-0	2018	A receptor tyrosine kinase ROR1 inhibitor (KAN0439834) induced significant apoptosis of pancreatic cells which was enhanced by erlotinib and ibrutinib.	ibrutinib	141-150	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	27-31
29567142-8	2018	Ibrutinib treatment can reduce the phosphorylation level of grouper"s BTK.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	70-73
29899839-1	2018	PI3Kdelta (idelalisib) and BTK (ibrutinib) inhibitors have demonstrated significant clinical activity in chronic lymphocytic leukemia (CLL) interfering with the cross-talk between CLL cells and the lymph node microenviroment, yet their mechanism of action remains to be fully elucidated.	ibrutinib	32-41	Bruton tyrosine kinase	Homo sapiens	27-30
29715023-1	2018	An alternative medicinal chemistry approach was conducted on Bruton"s tyrosine kinase (BTK) inhibitor 1 (ibrutinib) by merging the pyrazolo[3,4- d]pyrimidine component into a tricyclic skeleton.	ibrutinib	105-114	Bruton tyrosine kinase	Homo sapiens	61-85
29715023-1	2018	An alternative medicinal chemistry approach was conducted on Bruton"s tyrosine kinase (BTK) inhibitor 1 (ibrutinib) by merging the pyrazolo[3,4- d]pyrimidine component into a tricyclic skeleton.	ibrutinib	105-114	Bruton tyrosine kinase	Homo sapiens	87-90
29715023-1	2018	An alternative medicinal chemistry approach was conducted on Bruton"s tyrosine kinase (BTK) inhibitor 1 (ibrutinib) by merging the pyrazolo[3,4- d]pyrimidine component into a tricyclic skeleton.	ibrutinib	105-114	protein phosphatase 1 regulatory inhibitor subunit 1A	Homo sapiens	92-103
29848664-0	2018	Ibrutinib inactivates BMX-STAT3 in glioma stem cells to impair malignant growth and radioresistance.	ibrutinib	0-9	BMX non-receptor tyrosine kinase	Homo sapiens	22-25
29848664-0	2018	Ibrutinib inactivates BMX-STAT3 in glioma stem cells to impair malignant growth and radioresistance.	ibrutinib	0-9	signal transducer and activator of transcription 3	Homo sapiens	26-31
29848664-5	2018	We demonstrate that BMX inhibition by ibrutinib potently disrupts GSCs, suppresses GBM malignant growth, and effectively combines with radiotherapy.	ibrutinib	38-47	BMX non-receptor tyrosine kinase	Homo sapiens	20-23
29848664-6	2018	Ibrutinib markedly disrupts the BMX-mediated STAT3 activation in GSCs but shows minimal effect on neural progenitor cells (NPCs) lacking BMX expression.	ibrutinib	0-9	BMX non-receptor tyrosine kinase	Homo sapiens	32-35
29848664-6	2018	Ibrutinib markedly disrupts the BMX-mediated STAT3 activation in GSCs but shows minimal effect on neural progenitor cells (NPCs) lacking BMX expression.	ibrutinib	0-9	signal transducer and activator of transcription 3	Homo sapiens	45-50
29848664-7	2018	Mechanistically, BMX bypasses the suppressor of cytokine signaling 3 (SOCS3)-mediated inhibition of Janus kinase 2 (JAK2), whereas NPCs dampen the JAK2-mediated STAT3 activation via the negative regulation by SOCS3, providing a molecular basis for targeting BMX by ibrutinib to specifically eliminate GSCs while preserving NPCs.	ibrutinib	265-274	BMX non-receptor tyrosine kinase	Homo sapiens	17-20
30231317-6	2018	The use of novel agents targeting components of the BCR pathway, namely the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, and immunomodulatory drugs (IMIDs) like lenalidomide and pomalidomide, has so far been limited to patients who have recurrent/refractory PCNSL with promising high response rates.	ibrutinib	115-124	Bruton tyrosine kinase	Homo sapiens	76-98
29260925-5	2018	Recent clinical data suggest that novel agents targeting this pathway, including the Bruton"s tyrosine kinase inhibitor, ibrutinib, show significant promise in treatment of relapsed MZL.	ibrutinib	121-130	Bruton tyrosine kinase	Homo sapiens	85-109
29872501-0	2018	Cirmtuzumab inhibits ibrutinib-resistant, Wnt5a-induced Rac1 activation and proliferation in mantle cell lymphoma.	ibrutinib	21-30	Wnt family member 5A	Homo sapiens	42-47
29872501-0	2018	Cirmtuzumab inhibits ibrutinib-resistant, Wnt5a-induced Rac1 activation and proliferation in mantle cell lymphoma.	ibrutinib	21-30	Rac family small GTPase 1	Homo sapiens	56-60
29872501-1	2018	Cirmtuzumab may enhance the therapeutic activity of ibrutinib by inhibiting ROR1-dependent signaling pathway in patients with chronic lymphocytic leukemia (CLL).	ibrutinib	52-61	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	76-80
29496671-0	2018	BTKCys481Ser drives ibrutinib resistance via ERK1/2 and protects BTKwild-type MYD88-mutated cells by a paracrine mechanism.	ibrutinib	20-29	mitogen-activated protein kinase 3	Homo sapiens	45-51
29496671-0	2018	BTKCys481Ser drives ibrutinib resistance via ERK1/2 and protects BTKwild-type MYD88-mutated cells by a paracrine mechanism.	ibrutinib	20-29	MYD88 innate immune signal transduction adaptor	Homo sapiens	78-83
29496671-1	2018	Acquired ibrutinib resistance due to BTKCys481 mutations occurs in B-cell malignancies, including those with MYD88 mutations.	ibrutinib	9-18	MYD88 innate immune signal transduction adaptor	Homo sapiens	109-114
29496671-4	2018	We therefore engineered BTKCys481Ser and BTKWT expressing MYD88-mutated Waldenstrom macroglobulinemia (WM) and activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL) cells and observed reactivation of BTK-PLCgamma2-ERK1/2 signaling in the presence of ibrutinib in only the former.	ibrutinib	257-266	Bruton tyrosine kinase	Homo sapiens	24-27
29496671-5	2018	Use of ERK1/2 inhibitors triggered apoptosis in BTKCys481Ser-expressing cells and showed synergistic cytotoxicity with ibrutinib.	ibrutinib	119-128	mitogen-activated protein kinase 3	Homo sapiens	7-13
29496671-6	2018	ERK1/2 reactivation in ibrutinib-treated BTKCys481Ser cells was accompanied by release of many prosurvival and inflammatory cytokines, including interleukin-6 (IL-6) and IL-10 that were also blocked by ERK1/2 inhibition.	ibrutinib	23-32	mitogen-activated protein kinase 3	Homo sapiens	0-6
29496671-6	2018	ERK1/2 reactivation in ibrutinib-treated BTKCys481Ser cells was accompanied by release of many prosurvival and inflammatory cytokines, including interleukin-6 (IL-6) and IL-10 that were also blocked by ERK1/2 inhibition.	ibrutinib	23-32	interleukin 6	Homo sapiens	145-158
29496671-6	2018	ERK1/2 reactivation in ibrutinib-treated BTKCys481Ser cells was accompanied by release of many prosurvival and inflammatory cytokines, including interleukin-6 (IL-6) and IL-10 that were also blocked by ERK1/2 inhibition.	ibrutinib	23-32	interleukin 6	Homo sapiens	160-164
29496671-6	2018	ERK1/2 reactivation in ibrutinib-treated BTKCys481Ser cells was accompanied by release of many prosurvival and inflammatory cytokines, including interleukin-6 (IL-6) and IL-10 that were also blocked by ERK1/2 inhibition.	ibrutinib	23-32	interleukin 10	Homo sapiens	170-175
29496671-6	2018	ERK1/2 reactivation in ibrutinib-treated BTKCys481Ser cells was accompanied by release of many prosurvival and inflammatory cytokines, including interleukin-6 (IL-6) and IL-10 that were also blocked by ERK1/2 inhibition.	ibrutinib	23-32	mitogen-activated protein kinase 3	Homo sapiens	202-208
29496671-7	2018	To clarify if cytokine release by ibrutinib-treated BTKCys481Ser cells could protect BTKWT MYD88-mutated malignant cells, we used a Transwell coculture system and showed that nontransduced BTKWT MYD88-mutated WM or ABC DLBCL cells were rescued from ibrutinib-induced killing when cocultured with BTKCys481Ser but not their BTKWT-expressing counterparts.	ibrutinib	34-43	MYD88 innate immune signal transduction adaptor	Homo sapiens	91-96
29496671-7	2018	To clarify if cytokine release by ibrutinib-treated BTKCys481Ser cells could protect BTKWT MYD88-mutated malignant cells, we used a Transwell coculture system and showed that nontransduced BTKWT MYD88-mutated WM or ABC DLBCL cells were rescued from ibrutinib-induced killing when cocultured with BTKCys481Ser but not their BTKWT-expressing counterparts.	ibrutinib	34-43	MYD88 innate immune signal transduction adaptor	Homo sapiens	195-200
29496671-10	2018	Our findings show that the BTKCys481Ser mutation drives ibrutinib resistance in MYD88-mutated WM and ABC DLBCL cells through reactivation of ERK1/2 and can confer a protective effect on BTKWT cells through a paracrine mechanism.	ibrutinib	56-65	MYD88 innate immune signal transduction adaptor	Homo sapiens	80-85
29496671-10	2018	Our findings show that the BTKCys481Ser mutation drives ibrutinib resistance in MYD88-mutated WM and ABC DLBCL cells through reactivation of ERK1/2 and can confer a protective effect on BTKWT cells through a paracrine mechanism.	ibrutinib	56-65	mitogen-activated protein kinase 3	Homo sapiens	141-147
29359797-2	2018	Ibrutinib is an inhibitor of Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	29-51
29359797-2	2018	Ibrutinib is an inhibitor of Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	53-56
29587203-0	2018	Inhibitor of Bruton"s tyrosine kinases, PCI-32765, decreases pro-inflammatory mediators" production in high glucose-induced macrophages.	ibrutinib	40-49	Bruton tyrosine kinase	Homo sapiens	13-38
29724297-5	2018	Further study showed that ibrutinib treatment increased ERS-related protein expression, including Bip, ATF4 and CHOP, suggesting the induction of ER-stress in Reh cells.	ibrutinib	26-35	growth differentiation factor 10	Homo sapiens	98-101
29483220-0	2018	p110alpha Inhibition Overcomes Stromal Cell-Mediated Ibrutinib Resistance in Mantle Cell Lymphoma.	ibrutinib	53-62	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Mus musculus	0-9
29483220-1	2018	Acquired resistance to cancer drugs is common, also for modern targeted drugs like the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, a new drug approved for the treatment of the highly aggressive and relapsing mantle cell lymphoma (MCL).	ibrutinib	126-135	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	87-109
29483220-1	2018	Acquired resistance to cancer drugs is common, also for modern targeted drugs like the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, a new drug approved for the treatment of the highly aggressive and relapsing mantle cell lymphoma (MCL).	ibrutinib	126-135	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	111-114
29483220-3	2018	Here, we demonstrate that stromal cells protect MCL cells from ibrutinib-induced apoptosis and support MCL cell regrowth after drug removal by impairing ibrutinib-mediated downregulation of PI3K/AKT signaling.	ibrutinib	153-162	thymoma viral proto-oncogene 1	Mus musculus	195-198
29483220-4	2018	Importantly, the stromal cell-mediated ibrutinib resistance was overcome in vitro by inhibiting AKT activity using the PI3K catalytic p110alpha subunit-specific inhibitor BYL719.	ibrutinib	39-48	thymoma viral proto-oncogene 1	Mus musculus	96-99
29483220-4	2018	Importantly, the stromal cell-mediated ibrutinib resistance was overcome in vitro by inhibiting AKT activity using the PI3K catalytic p110alpha subunit-specific inhibitor BYL719.	ibrutinib	39-48	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Mus musculus	134-143
29483220-6	2018	Furthermore, inhibition of p110alpha activity by BYL719 potentiated the ability of ibrutinib to inhibit MCL tumor growth in vivo in a mouse xenograft model.	ibrutinib	83-92	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Mus musculus	27-36
29483220-8	2018	This suggests that combined treatment with ibrutinib and a p110alpha inhibitor, alternatively by disrupting stromal cell-MCL cell interaction, may be a promising therapeutic strategy to overcome stromal cell-mediated ibrutinib resistance in MCL.	ibrutinib	217-226	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Mus musculus	59-68
29724297-5	2018	Further study showed that ibrutinib treatment increased ERS-related protein expression, including Bip, ATF4 and CHOP, suggesting the induction of ER-stress in Reh cells.	ibrutinib	26-35	activating transcription factor 4	Homo sapiens	103-107
29724297-5	2018	Further study showed that ibrutinib treatment increased ERS-related protein expression, including Bip, ATF4 and CHOP, suggesting the induction of ER-stress in Reh cells.	ibrutinib	26-35	DNA damage inducible transcript 3	Homo sapiens	112-116
29669753-1	2018	Ibrutinib has previously been shown to inhibit Bruton"s tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK), which mediate B-cell and T-cell receptor signaling, respectively.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	47-71
29437592-10	2018	These results demonstrate sustained efficacy and acceptable tolerability of ibrutinib over an extended time, providing the longest experience for Bruton tyrosine kinase inhibitor treatment in patients with CLL/SLL.	ibrutinib	76-85	Bruton tyrosine kinase	Homo sapiens	146-168
29437592-10	2018	These results demonstrate sustained efficacy and acceptable tolerability of ibrutinib over an extended time, providing the longest experience for Bruton tyrosine kinase inhibitor treatment in patients with CLL/SLL.	ibrutinib	76-85	solute carrier family 35 member B2	Homo sapiens	210-213
29437592-1	2018	We previously reported durable responses and manageable safety of ibrutinib from a 3-year follow-up of treatment-naive (TN) older patients (&gt;=65 years of age) and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).	ibrutinib	66-75	solute carrier family 35 member B2	Homo sapiens	267-270
29437592-6	2018	Median PFS in R/R patients was 51 months; in those with del(11q), del(17p), and unmutated IGHV, it was 51, 26, and 43 months, respectively, demonstrating long-term efficacy of ibrutinib in some high-risk subgroups.	ibrutinib	176-185	immunoglobulin heavy variable 3-69-1 (pseudogene)	Homo sapiens	90-94
29669753-1	2018	Ibrutinib has previously been shown to inhibit Bruton"s tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK), which mediate B-cell and T-cell receptor signaling, respectively.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	73-76
29669753-1	2018	Ibrutinib has previously been shown to inhibit Bruton"s tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK), which mediate B-cell and T-cell receptor signaling, respectively.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	82-119
29669753-1	2018	Ibrutinib has previously been shown to inhibit Bruton"s tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK), which mediate B-cell and T-cell receptor signaling, respectively.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	121-124
29669753-2	2018	BTK inhibition with ibrutinib has demonstrated impressive clinical responses in a variety of B-cell malignancies.	ibrutinib	20-29	Bruton tyrosine kinase	Homo sapiens	0-3
29669753-3	2018	Whether ibrutinib inhibition of ITK can lead to clinical response in T-cell malignancies is unknown.	ibrutinib	8-17	IL2 inducible T cell kinase	Homo sapiens	32-35
29669753-4	2018	We hypothesized that ibrutinib-mediated ITK inhibition in T-cell lymphoma would result in decreased signaling through the T-cell receptor pathway and promote antitumor immune response by driving selective cytotoxic Th1 CD4 effector T-cell differentiation.	ibrutinib	21-30	IL2 inducible T cell kinase	Homo sapiens	40-43
29669753-11	2018	Our data suggest that ibrutinib inhibition of ITK has limited clinical activity in T-cell lymphoma.	ibrutinib	22-31	IL2 inducible T cell kinase	Homo sapiens	46-49
29398709-0	2018	Ibrutinib inhibition of ERBB4 reduces cell growth in a WNT5A-dependent manner.	ibrutinib	0-9	erb-b2 receptor tyrosine kinase 4	Mus musculus	24-29
29476222-2	2018	Ibrutinib, an orally administered Bruton"s tyrosine kinase (BTK) inhibitor, has shown substantial activity in CLL or MCL patients with CNS localization, and in primary central nervous system lymphoma (PCNSL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	34-58
29476222-2	2018	Ibrutinib, an orally administered Bruton"s tyrosine kinase (BTK) inhibitor, has shown substantial activity in CLL or MCL patients with CNS localization, and in primary central nervous system lymphoma (PCNSL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	60-63
29480432-3	2018	RECENT FINDINGS: Ibrutinib was FDA-approved for the upfront treatment of CLL in 2016 after being studied in older patients and those with 17p deletions or TP53 mutations.	ibrutinib	17-26	tumor protein p53	Homo sapiens	155-159
28972595-0	2018	Ibrutinib modulates the immunosuppressive CLL microenvironment through STAT3-mediated suppression of regulatory B-cell function and inhibition of the PD-1/PD-L1 pathway.	ibrutinib	0-9	signal transducer and activator of transcription 3	Homo sapiens	71-76
28972595-0	2018	Ibrutinib modulates the immunosuppressive CLL microenvironment through STAT3-mediated suppression of regulatory B-cell function and inhibition of the PD-1/PD-L1 pathway.	ibrutinib	0-9	CD274 molecule	Homo sapiens	155-160
28972595-1	2018	Ibrutinib, a covalent inhibitor of Bruton Tyrosine Kinase (BTK), is approved for treatment of patients with relapsed/refractory or treatment-naive chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	59-62
28972595-2	2018	Besides directly inhibiting BTK, ibrutinib possesses immunomodulatory properties through targeting multiple signaling pathways.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	28-31
28972595-5	2018	In peripheral blood samples collected prospectively from CLL patients treated with ibrutinib monotherapy, we observed selective and durable downregulation of PD-L1 on CLL cells by 3 months post-treatment.	ibrutinib	83-92	CD274 molecule	Homo sapiens	158-163
28972595-8	2018	We also demonstrated reduced interleukin (IL)-10 production by CLL cells in patients receiving ibrutinib, which was also linked to suppression of STAT3 phosphorylation.	ibrutinib	95-104	interleukin 10	Homo sapiens	29-48
28972595-8	2018	We also demonstrated reduced interleukin (IL)-10 production by CLL cells in patients receiving ibrutinib, which was also linked to suppression of STAT3 phosphorylation.	ibrutinib	95-104	signal transducer and activator of transcription 3	Homo sapiens	146-151
28972595-9	2018	Taken together, these findings provide a mechanistic basis for immunomodulation by ibrutinib through inhibition of the STAT3 pathway, critical in inducing and sustaining tumor immune tolerance.	ibrutinib	83-92	signal transducer and activator of transcription 3	Homo sapiens	119-124
29117640-0	2018	Functional Characterization of 22 CYP3A4 Protein Variants to Metabolize Ibrutinib In Vitro.	ibrutinib	72-81	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	34-40
29117640-3	2018	Ibrutinib is an anticancer drug and primarily metabolized by CYP3A4.	ibrutinib	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	61-67
29117640-4	2018	The aim of this study was to systematically investigate the effects of 22 CYP3A4 protein variants on the metabolism of ibrutinib in vitro.	ibrutinib	119-128	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	74-80
29117640-6	2018	As the first study of 22 CYP3A4 protein variants in ibrutinib metabolism, these comprehensive data may help in the clinical assessment of the metabolism and elimination of ibrutinib and also offer a reference to the personalized treatment of ibrutinib in clinic.	ibrutinib	52-61	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	25-31
29117640-6	2018	As the first study of 22 CYP3A4 protein variants in ibrutinib metabolism, these comprehensive data may help in the clinical assessment of the metabolism and elimination of ibrutinib and also offer a reference to the personalized treatment of ibrutinib in clinic.	ibrutinib	172-181	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	25-31
29117640-6	2018	As the first study of 22 CYP3A4 protein variants in ibrutinib metabolism, these comprehensive data may help in the clinical assessment of the metabolism and elimination of ibrutinib and also offer a reference to the personalized treatment of ibrutinib in clinic.	ibrutinib	172-181	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	25-31
29285806-0	2018	Systematic review of infectious events with the Bruton tyrosine kinase inhibitor ibrutinib in the treatment of hematologic malignancies.	ibrutinib	81-90	Bruton tyrosine kinase	Homo sapiens	48-70
29285806-1	2018	OBJECTIVE: Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK) in B lymphocytes as well as other kinases including interleukin-2-inducible T-cell kinase (ITK) in CD4+ Th2 regulatory T cells.	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	53-75
29285806-1	2018	OBJECTIVE: Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK) in B lymphocytes as well as other kinases including interleukin-2-inducible T-cell kinase (ITK) in CD4+ Th2 regulatory T cells.	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	77-80
29285806-1	2018	OBJECTIVE: Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK) in B lymphocytes as well as other kinases including interleukin-2-inducible T-cell kinase (ITK) in CD4+ Th2 regulatory T cells.	ibrutinib	11-20	IL2 inducible T cell kinase	Homo sapiens	173-176
29285806-1	2018	OBJECTIVE: Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK) in B lymphocytes as well as other kinases including interleukin-2-inducible T-cell kinase (ITK) in CD4+ Th2 regulatory T cells.	ibrutinib	11-20	CD4 molecule	Homo sapiens	181-184
29398709-0	2018	Ibrutinib inhibition of ERBB4 reduces cell growth in a WNT5A-dependent manner.	ibrutinib	0-9	wingless-type MMTV integration site family, member 5A	Mus musculus	55-60
29398709-4	2018	Using a unique functional protein microarray platform, we found that ibrutinib inhibits ERBB4 activity in the same nM range as its canonical target, BTK.	ibrutinib	69-78	erb-b2 receptor tyrosine kinase 4	Mus musculus	88-93
29398709-4	2018	Using a unique functional protein microarray platform, we found that ibrutinib inhibits ERBB4 activity in the same nM range as its canonical target, BTK.	ibrutinib	69-78	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	149-152
29398709-5	2018	Cell-based assays revealed that ibrutinib treatment inhibited cell growth and decreased phosphorylation of ERBB4 and downstream targets MEK and ERK in cancer cell lines with high levels of endogenous ERBB4.	ibrutinib	32-41	erb-b2 receptor tyrosine kinase 4	Mus musculus	107-112
29398709-5	2018	Cell-based assays revealed that ibrutinib treatment inhibited cell growth and decreased phosphorylation of ERBB4 and downstream targets MEK and ERK in cancer cell lines with high levels of endogenous ERBB4.	ibrutinib	32-41	midkine	Mus musculus	136-139
29398709-5	2018	Cell-based assays revealed that ibrutinib treatment inhibited cell growth and decreased phosphorylation of ERBB4 and downstream targets MEK and ERK in cancer cell lines with high levels of endogenous ERBB4.	ibrutinib	32-41	mitogen-activated protein kinase 1	Mus musculus	144-147
29398709-5	2018	Cell-based assays revealed that ibrutinib treatment inhibited cell growth and decreased phosphorylation of ERBB4 and downstream targets MEK and ERK in cancer cell lines with high levels of endogenous ERBB4.	ibrutinib	32-41	erb-b2 receptor tyrosine kinase 4	Mus musculus	200-205
29398709-9	2018	Moreover, inhibition of WNT5A expression led to an ibrutinib response in non-responsive cell lines.	ibrutinib	51-60	wingless-type MMTV integration site family, member 5A	Mus musculus	24-29
29441438-3	2018	The BTK inhibitor ibrutinib has been approved as a therapy for refractory MCL, and while it shows some clinical activity, patients frequently develop primary or secondary ibrutinib resistance and have very poor outcomes after relapsing following ibrutinib treatment.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
29441438-3	2018	The BTK inhibitor ibrutinib has been approved as a therapy for refractory MCL, and while it shows some clinical activity, patients frequently develop primary or secondary ibrutinib resistance and have very poor outcomes after relapsing following ibrutinib treatment.	ibrutinib	171-180	Bruton tyrosine kinase	Homo sapiens	4-7
29581109-6	2018	Aging Tet2-deficient mice accumulate clonal CD19+ B220low immunoglobulin M+ B-cell populations with transplantable ability showing similarities to human chronic lymphocytic leukemia, including CD5 expression and sensitivity to ibrutinib-mediated B-cell receptor (BCR) signaling inhibition.	ibrutinib	227-236	tet methylcytosine dioxygenase 2	Mus musculus	6-10
29441438-3	2018	The BTK inhibitor ibrutinib has been approved as a therapy for refractory MCL, and while it shows some clinical activity, patients frequently develop primary or secondary ibrutinib resistance and have very poor outcomes after relapsing following ibrutinib treatment.	ibrutinib	171-180	Bruton tyrosine kinase	Homo sapiens	4-7
29452660-4	2018	Inhibition of Bruton"s tyrosine kinase, an essential B-cell receptor pathway component with ibrutinib has shown clinical activity and has changed how MCL is treated in the relapsed/refractory setting.	ibrutinib	92-101	Bruton tyrosine kinase	Homo sapiens	14-38
29590547-1	2018	BACKGROUND: Both the BTK inhibitor ibrutinib and the BCL2 inhibitor venetoclax are active as monotherapy in the treatment of mantle-cell lymphoma.	ibrutinib	35-44	Bruton tyrosine kinase	Homo sapiens	21-24
29590547-19	2018	CONCLUSIONS: In this study involving historical controls, dual targeting of BTK and BCL2 with ibrutinib and venetoclax was consistent with improved outcomes in patients with mantle-cell lymphoma who had been predicted to have poor outcomes with current therapy.	ibrutinib	94-103	Bruton tyrosine kinase	Homo sapiens	76-79
29590547-19	2018	CONCLUSIONS: In this study involving historical controls, dual targeting of BTK and BCL2 with ibrutinib and venetoclax was consistent with improved outcomes in patients with mantle-cell lymphoma who had been predicted to have poor outcomes with current therapy.	ibrutinib	94-103	BCL2 apoptosis regulator	Homo sapiens	84-88
29750146-3	2018	The cytotoxicity owing to alloreactivity was less susceptible to interference by KI than the ADCC of anti-CD20 mAbs, which was markedly diminished by ibrutinib, but not by idelalisib.	ibrutinib	150-159	keratin 20	Homo sapiens	106-110
29750146-5	2018	Irreversible BTK inhibitors at a clinically relevant concentration of 1 muM only weakly impaired the ADCC of anti-CD20 mAbs, with less influence in combinations with obinutuzumab than with rituximab and by acalabrutinib than by ibrutinib or tirabrutinib.	ibrutinib	228-237	Bruton tyrosine kinase	Homo sapiens	13-16
29381098-0	2018	Are BTK and PLCG2 mutations necessary and sufficient for ibrutinib resistance in chronic lymphocytic leukemia?	ibrutinib	57-66	Bruton tyrosine kinase	Homo sapiens	4-7
29383704-4	2018	We have recently identified platelet TLR4, NLRP3, and Bruton tyrosine kinase (BTK) as critical regulators of platelet aggregation and thrombus formation, suggesting that the BTK inhibitor ibrutinib is a potential therapeutic target.	ibrutinib	188-197	toll like receptor 4	Homo sapiens	37-41
29383704-4	2018	We have recently identified platelet TLR4, NLRP3, and Bruton tyrosine kinase (BTK) as critical regulators of platelet aggregation and thrombus formation, suggesting that the BTK inhibitor ibrutinib is a potential therapeutic target.	ibrutinib	188-197	NLR family pyrin domain containing 3	Homo sapiens	43-48
29383704-4	2018	We have recently identified platelet TLR4, NLRP3, and Bruton tyrosine kinase (BTK) as critical regulators of platelet aggregation and thrombus formation, suggesting that the BTK inhibitor ibrutinib is a potential therapeutic target.	ibrutinib	188-197	Bruton tyrosine kinase	Homo sapiens	54-76
29383704-4	2018	We have recently identified platelet TLR4, NLRP3, and Bruton tyrosine kinase (BTK) as critical regulators of platelet aggregation and thrombus formation, suggesting that the BTK inhibitor ibrutinib is a potential therapeutic target.	ibrutinib	188-197	Bruton tyrosine kinase	Homo sapiens	78-81
29383704-4	2018	We have recently identified platelet TLR4, NLRP3, and Bruton tyrosine kinase (BTK) as critical regulators of platelet aggregation and thrombus formation, suggesting that the BTK inhibitor ibrutinib is a potential therapeutic target.	ibrutinib	188-197	Bruton tyrosine kinase	Homo sapiens	174-177
28549767-2	2018	Ibrutinib, an inhibitor of Bruton"s tyrosine kinase, has demonstrated impressive response rates in the relapsed/refractory setting, including in the setting of Del17p and/or TP53 mutations.	ibrutinib	0-9	tumor protein p53	Homo sapiens	174-178
29381098-0	2018	Are BTK and PLCG2 mutations necessary and sufficient for ibrutinib resistance in chronic lymphocytic leukemia?	ibrutinib	57-66	phospholipase C gamma 2	Homo sapiens	12-17
29381098-1	2018	INTRODUCTION: Ibrutinib is the first BTK inhibitor to show efficacy in chronic lymphocytic leukemia (CLL) and is also the first BTK inhibitor to which patients have developed resistance.	ibrutinib	14-23	Bruton tyrosine kinase	Homo sapiens	37-40
29381098-1	2018	INTRODUCTION: Ibrutinib is the first BTK inhibitor to show efficacy in chronic lymphocytic leukemia (CLL) and is also the first BTK inhibitor to which patients have developed resistance.	ibrutinib	14-23	Bruton tyrosine kinase	Homo sapiens	128-131
29381098-2	2018	Mutations in BTK and PLCG2 are found in  80% of CLL patients with acquired resistance to ibrutinib, but it remains unclear if these mutations are merely associated with disease relapse or directly cause it.	ibrutinib	89-98	Bruton tyrosine kinase	Homo sapiens	13-16
29381098-2	2018	Mutations in BTK and PLCG2 are found in  80% of CLL patients with acquired resistance to ibrutinib, but it remains unclear if these mutations are merely associated with disease relapse or directly cause it.	ibrutinib	89-98	phospholipase C gamma 2	Homo sapiens	21-26
29381098-6	2018	Expert commentary: While BTK/PLCG2 mutations have characteristics suggesting that they can drive ibrutinib resistance, this conclusion remains formally unproven until specific inhibition of such mutations is shown to cause regression of ibrutinib-resistant CLL.	ibrutinib	97-106	Bruton tyrosine kinase	Homo sapiens	25-28
29381098-6	2018	Expert commentary: While BTK/PLCG2 mutations have characteristics suggesting that they can drive ibrutinib resistance, this conclusion remains formally unproven until specific inhibition of such mutations is shown to cause regression of ibrutinib-resistant CLL.	ibrutinib	97-106	phospholipase C gamma 2	Homo sapiens	29-34
29381098-6	2018	Expert commentary: While BTK/PLCG2 mutations have characteristics suggesting that they can drive ibrutinib resistance, this conclusion remains formally unproven until specific inhibition of such mutations is shown to cause regression of ibrutinib-resistant CLL.	ibrutinib	237-246	Bruton tyrosine kinase	Homo sapiens	25-28
29326436-6	2018	We also show that ibrutinib, a Btk inhibitor that promotes leukemic cell mobilization from lymphoid organs, reverses the CXCR4/CCR7 recycling abnormalities in CLL cells by increasing p66Shc expression.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	31-34
29482771-1	2018	Authors" Reply to the Letter to the Editor by Y. Lynn Wang (MYD88 mutations and sensitivity to ibrutinib therapy).	ibrutinib	95-104	MYD88 innate immune signal transduction adaptor	Homo sapiens	60-65
28695755-0	2018	Ibrutinib therapy is effective in B-cell prolymphocytic leukemia exhibiting MYC aberrations.	ibrutinib	0-9	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	76-79
28696801-7	2018	Compared to their previous chemoimmunotherapy patients receiving salvage ibrutinib therapy (n = 47) had a significantly increased risk of a major infection (IRR 2.35 95% CI 1.27, 4.34).	ibrutinib	73-82	insulin receptor related receptor	Homo sapiens	157-160
29326436-6	2018	We also show that ibrutinib, a Btk inhibitor that promotes leukemic cell mobilization from lymphoid organs, reverses the CXCR4/CCR7 recycling abnormalities in CLL cells by increasing p66Shc expression.	ibrutinib	18-27	C-X-C motif chemokine receptor 4	Homo sapiens	121-126
29326436-6	2018	We also show that ibrutinib, a Btk inhibitor that promotes leukemic cell mobilization from lymphoid organs, reverses the CXCR4/CCR7 recycling abnormalities in CLL cells by increasing p66Shc expression.	ibrutinib	18-27	C-C motif chemokine receptor 7	Homo sapiens	127-131
29326436-7	2018	These results, identifying p66Shc as a regulator of CXCR4/CCR7 recycling in B cells, underscore the relevance of its deficiency to CLL pathogenesis and provide new clues to the mechanisms underlying the therapeutic effects of ibrutinib.	ibrutinib	226-235	C-X-C motif chemokine receptor 4	Homo sapiens	52-57
29326436-7	2018	These results, identifying p66Shc as a regulator of CXCR4/CCR7 recycling in B cells, underscore the relevance of its deficiency to CLL pathogenesis and provide new clues to the mechanisms underlying the therapeutic effects of ibrutinib.	ibrutinib	226-235	C-C motif chemokine receptor 7	Homo sapiens	58-62
29455639-5	2018	In particular, the orally administered irreversible BTK inhibitor ibrutinib is associated with high response rates in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and mantle-cell lymphoma (MCL), including patients with high-risk genetic lesions.	ibrutinib	66-75	Bruton tyrosine kinase	Homo sapiens	52-55
29484684-3	2018	Recently, ibrutinib was approved for patients with relapsed/refractory CLL or for untreated CLL patients with del 17p or TP53 mutation.	ibrutinib	10-19	tumor protein p53	Homo sapiens	121-125
28753229-0	2018	Rapid decline in insulin antibodies and glutamic acid decarboxylase autoantibodies with ibrutinib therapy of chronic lymphocytic leukaemia.	ibrutinib	88-97	insulin	Homo sapiens	17-24
29398441-4	2018	When tested in an ABC-DLBCL model with a dual MyD88/CD79 mutation (OCI-LY10), 30 demonstrated tumour regressions in combination with ibrutinib.	ibrutinib	133-142	MYD88 innate immune signal transduction adaptor	Homo sapiens	46-51
29398648-1	2018	BACKGROUND: Ibrutinib shows superiority over obinutuzumab with chlorambucil (G-Clb) in untreated patients with chronic lymphocytic leukemia with comorbidities who cannot tolerate fludarabine-based therapy.	ibrutinib	12-21	citramalyl-CoA lyase	Homo sapiens	79-82
29347836-0	2018	Strategies to overcome resistance mutations of Bruton"s tyrosine kinase inhibitor ibrutinib.	ibrutinib	82-91	Bruton tyrosine kinase	Homo sapiens	47-71
29347836-1	2018	Ibrutinib, as the first Bruton"s tyrosine kinase (Btk) inhibitor, has been shown to have clinically significant activity in leukemias and lymphomas.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	24-48
29347836-1	2018	Ibrutinib, as the first Bruton"s tyrosine kinase (Btk) inhibitor, has been shown to have clinically significant activity in leukemias and lymphomas.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	50-53
29208667-6	2018	Ibrutinib was administrated in SCLC cells to verify its synergistic anti-tumor effect with chemotherapy using preclinical models including a PDX model.Results: Downregulation of Etk suppressed autophagy in chemoresistant SCLC cells, and direct inhibition of autophagy sensitized cells to chemotherapy.	ibrutinib	0-9	BMX non-receptor tyrosine kinase	Homo sapiens	178-181
29208667-8	2018	Furthermore, ibrutinib was found to exhibit a synergistic anti-tumor effect with chemotherapy in targeting Etk.Conclusions: Our results demonstrated for the first time that Etk interacts with PFKFB4 to promote SCLC chemoresistance through regulation of autophagy.	ibrutinib	13-22	BMX non-receptor tyrosine kinase	Homo sapiens	107-110
29208667-8	2018	Furthermore, ibrutinib was found to exhibit a synergistic anti-tumor effect with chemotherapy in targeting Etk.Conclusions: Our results demonstrated for the first time that Etk interacts with PFKFB4 to promote SCLC chemoresistance through regulation of autophagy.	ibrutinib	13-22	BMX non-receptor tyrosine kinase	Homo sapiens	173-176
29208667-8	2018	Furthermore, ibrutinib was found to exhibit a synergistic anti-tumor effect with chemotherapy in targeting Etk.Conclusions: Our results demonstrated for the first time that Etk interacts with PFKFB4 to promote SCLC chemoresistance through regulation of autophagy.	ibrutinib	13-22	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4	Homo sapiens	192-198
28753229-1	2018	WHAT IS KNOWN AND OBJECTIVE: Ibrutinib is inhibiting the Bruton"s tyrosine kinase (BTK), thereby influencing B-cell development.	ibrutinib	29-38	Bruton tyrosine kinase	Homo sapiens	57-81
28753229-1	2018	WHAT IS KNOWN AND OBJECTIVE: Ibrutinib is inhibiting the Bruton"s tyrosine kinase (BTK), thereby influencing B-cell development.	ibrutinib	29-38	Bruton tyrosine kinase	Homo sapiens	83-86
28753229-7	2018	Seven weeks after start of ibrutinib, his insulin antibodies level had dropped by 54.6%.	ibrutinib	27-36	insulin	Homo sapiens	42-49
28753229-9	2018	WHAT IS NEW AND CONCLUSION: The inhibitory effect of ibrutinib on the levels of insulin antibodies and glutamic acid decarboxylase autoantibodies is a novel finding and may have implications for diabetes care.	ibrutinib	53-62	insulin	Homo sapiens	80-87
28921505-0	2018	NFATC1 activation by DNA hypomethylation in chronic lymphocytic leukemia correlates with clinical staging and can be inhibited by ibrutinib.	ibrutinib	130-139	nuclear factor of activated T cells 1	Homo sapiens	0-6
28629235-1	2018	Ibrutinib is a Bruton"s tyrosine kinase (BTK) inhibitor finding increasingly widespread use in non-Hodgkin lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	15-39
28629235-1	2018	Ibrutinib is a Bruton"s tyrosine kinase (BTK) inhibitor finding increasingly widespread use in non-Hodgkin lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	41-44
28663582-4	2018	BET-PROTACs induce more apoptosis than BETi of MCL cells, including those resistant to ibrutinib.	ibrutinib	87-96	delta/notch-like EGF repeat containing	Mus musculus	0-3
29074501-2	2018	Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor approved for the treatment of several B-cell malignancies, showed promising activity in FL in a phase 1 study.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-35
29074501-2	2018	Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor approved for the treatment of several B-cell malignancies, showed promising activity in FL in a phase 1 study.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	37-40
29074501-9	2018	CARD11 mutations were present in 16% of patients (5 of 31) and predicted resistance to ibrutinib with only wild-type patients responding (P = .002).	ibrutinib	87-96	caspase recruitment domain family member 11	Homo sapiens	0-6
29074501-14	2018	Somatic mutations such as CARD11 may have an impact on response to ibrutinib, may inform clinical decisions, and should be evaluated in larger data sets.	ibrutinib	67-76	caspase recruitment domain family member 11	Homo sapiens	26-32
29632735-1	2018	Using next-generation immunoglobulin (IGH) sequencing and flow cytometry, we characterized the composition, diversity and dynamics of non-malignant B cells in patients undergoing treatment with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or chemo-immunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR).	ibrutinib	237-246	Bruton tyrosine kinase	Homo sapiens	198-220
29632735-2	2018	During ibrutinib therapy, non-malignant B cell numbers declined, but patients maintained stable IGH diversity and constant fractions of IGH-mutated B cells.	ibrutinib	7-16	immunoglobulin heavy locus	Homo sapiens	136-139
29146136-4	2018	Additionally, these pyrimidine derivatives also exhibited enhanced activity to block the proliferation of B-cell lymphoma cells compared with the representative BTK inhibitor ibrutinib.	ibrutinib	175-184	Bruton tyrosine kinase	Homo sapiens	161-164
28460620-11	2018	The CK2 inhibitor acted synergistically with either the SYK inhibitor Fostamatinib or the BTK inhibitor Ibrutinib in inducing DLBCL cell death.	ibrutinib	104-113	Bruton tyrosine kinase	Homo sapiens	90-93
29125406-1	2018	INTRODUCTION: The BTK inhibitor ibrutinib is effective in both low- and high-risk CLL patients, achieving durable remissions with continuous therapy in the majority of patients.	ibrutinib	32-41	Bruton tyrosine kinase	Homo sapiens	18-21
29424919-3	2018	Ibrutinib, a Bruton"s Tyrosine Kinase (BTK) inhibitor, is a new anticancer drug used to treat many cancers.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-37
29424919-3	2018	Ibrutinib, a Bruton"s Tyrosine Kinase (BTK) inhibitor, is a new anticancer drug used to treat many cancers.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	39-42
29122993-9	2018	Finally, we show improved sensitivity of stroma-supported CLL cells to NF-kappaB inhibition when combining the NF-kappaB inhibitor with the SYK inhibitor R406 or the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, agents known to inhibit the stroma-leukemia crosstalk.	ibrutinib	207-216	Bruton tyrosine kinase	Homo sapiens	166-190
29122993-9	2018	Finally, we show improved sensitivity of stroma-supported CLL cells to NF-kappaB inhibition when combining the NF-kappaB inhibitor with the SYK inhibitor R406 or the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, agents known to inhibit the stroma-leukemia crosstalk.	ibrutinib	207-216	Bruton tyrosine kinase	Homo sapiens	192-195
30069629-3	2018	Ibrutinib (PCI-32765) is a small molecule which serves as a covalent irreversible inhibitor of BTK.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	95-98
28905990-3	2018	Recently, several drugs that target the B-cell receptor (BCR) signaling pathway, especially the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicate that pharmacological inhibition of BCR pathway holds promise in MCL treatment.	ibrutinib	137-146	Bruton tyrosine kinase	Homo sapiens	96-120
28905990-3	2018	Recently, several drugs that target the B-cell receptor (BCR) signaling pathway, especially the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicate that pharmacological inhibition of BCR pathway holds promise in MCL treatment.	ibrutinib	137-146	Bruton tyrosine kinase	Homo sapiens	122-125
28905990-4	2018	Here, we have developed a novel irreversible BTK inhibitor, PLS-123, that has more potent and selective anti-tumor activity than ibrutinib in vitro and in vivo.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	45-48
30069636-2	2018	Ibrutinib, a first-in-class BTK inhibitor, has been approved for the treatment of distinct B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	28-31
30069636-3	2018	To overcome off-target side effects of and emerging resistances to ibrutinib, more selective second-generation BTK inhibitors were developed.	ibrutinib	67-76	Bruton tyrosine kinase	Homo sapiens	111-114
29246803-1	2018	BACKGROUND: Therapy targeting Bruton"s tyrosine kinase (BTK) with ibrutinib has transformed the treatment of chronic lymphocytic leukaemia.	ibrutinib	66-75	Bruton tyrosine kinase	Homo sapiens	30-54
29246803-1	2018	BACKGROUND: Therapy targeting Bruton"s tyrosine kinase (BTK) with ibrutinib has transformed the treatment of chronic lymphocytic leukaemia.	ibrutinib	66-75	Bruton tyrosine kinase	Homo sapiens	56-59
29320977-0	2018	Ibrutinib targets microRNA-21 in multiple myeloma cells by inhibiting NF-kappaB and STAT3.	ibrutinib	0-9	signal transducer and activator of transcription 3	Homo sapiens	84-89
29320977-4	2018	Moreover, ibrutinib attenuates microRNA-21 expression in multiple myeloma cells by inhibiting nuclear factor-kappaB and signal transducer and activator of transcription 3 signaling pathways.	ibrutinib	10-19	signal transducer and activator of transcription 3	Homo sapiens	120-170
28993409-0	2017	MALT1 Inhibition Is Efficacious in Both Naive and Ibrutinib-Resistant Chronic Lymphocytic Leukemia.	ibrutinib	50-59	MALT1 paracaspase	Homo sapiens	0-5
29317997-1	2018	Ibrutinib is the first in-class, orally administered, Bruton"s tyrosine kinase (BTK) inhibitor that abrogates the critical signaling downstream of the B-cell receptor (BCR).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	54-78
29317997-1	2018	Ibrutinib is the first in-class, orally administered, Bruton"s tyrosine kinase (BTK) inhibitor that abrogates the critical signaling downstream of the B-cell receptor (BCR).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	80-83
28993409-2	2017	The ibrutinib target, Bruton"s tyrosine kinase (BTK), is essential for B-cell receptor signaling, and most resistant cases carry mutations in BTK or PLCG2, a downstream effector target of BTK.	ibrutinib	4-13	Bruton tyrosine kinase	Homo sapiens	22-46
28993409-2	2017	The ibrutinib target, Bruton"s tyrosine kinase (BTK), is essential for B-cell receptor signaling, and most resistant cases carry mutations in BTK or PLCG2, a downstream effector target of BTK.	ibrutinib	4-13	Bruton tyrosine kinase	Homo sapiens	48-51
28993409-2	2017	The ibrutinib target, Bruton"s tyrosine kinase (BTK), is essential for B-cell receptor signaling, and most resistant cases carry mutations in BTK or PLCG2, a downstream effector target of BTK.	ibrutinib	4-13	Bruton tyrosine kinase	Homo sapiens	142-145
28993409-2	2017	The ibrutinib target, Bruton"s tyrosine kinase (BTK), is essential for B-cell receptor signaling, and most resistant cases carry mutations in BTK or PLCG2, a downstream effector target of BTK.	ibrutinib	4-13	phospholipase C gamma 2	Homo sapiens	149-154
28993409-2	2017	The ibrutinib target, Bruton"s tyrosine kinase (BTK), is essential for B-cell receptor signaling, and most resistant cases carry mutations in BTK or PLCG2, a downstream effector target of BTK.	ibrutinib	4-13	Bruton tyrosine kinase	Homo sapiens	142-145
28993409-8	2017	Overall, our findings provide a preclinical rationale for the clinical development of MALT1 inhibitors in CLL, in particular for ibrutinib-resistant forms of this disease.	ibrutinib	129-138	MALT1 paracaspase	Homo sapiens	86-91
29222275-7	2017	TP53 disruption by gene mutation and/or deletion associates with chemoimmunotherapy failure and mandates treatment with innovative drugs, including ibrutinib, idelalisib, or venetoclax.	ibrutinib	148-157	tumor protein p53	Homo sapiens	0-4
29296914-1	2017	The Bruton tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	4-26
29296914-1	2017	The Bruton tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	28-31
29296914-2	2017	Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side effects of ibrutinib.	ibrutinib	105-114	tec protein tyrosine kinase	Homo sapiens	25-28
29365396-11	2017	Ibrutinib could inhibit the secretion of CXCL12 (SUDHL10: 660 pg/ml vs 1 400 pg/ml, P=0.004; HBL-1: 720 pg/ml vs 1 490 pg/ml, P=0.018; DLBCL:850 pg/ml vs 1 450 pg/ml, P=0.004) and expression of CXCR4 (P&lt;0.05) .	ibrutinib	0-9	C-X-C motif chemokine ligand 12	Homo sapiens	41-47
29365396-11	2017	Ibrutinib could inhibit the secretion of CXCL12 (SUDHL10: 660 pg/ml vs 1 400 pg/ml, P=0.004; HBL-1: 720 pg/ml vs 1 490 pg/ml, P=0.018; DLBCL:850 pg/ml vs 1 450 pg/ml, P=0.004) and expression of CXCR4 (P&lt;0.05) .	ibrutinib	0-9	C-X-C motif chemokine receptor 4	Homo sapiens	194-199
29365396-16	2017	But after transfected with a CXCR4-lentivector, the overexpression of CXCR4 was detected and the ratio of apoptosis was significantly lower when co-cultured with MSC which demonstrated that ibrutinib inhibited drug-resistance by inhibiting the expression of CXCR4.	ibrutinib	190-199	C-X-C motif chemokine receptor 4	Homo sapiens	29-34
29365396-16	2017	But after transfected with a CXCR4-lentivector, the overexpression of CXCR4 was detected and the ratio of apoptosis was significantly lower when co-cultured with MSC which demonstrated that ibrutinib inhibited drug-resistance by inhibiting the expression of CXCR4.	ibrutinib	190-199	C-X-C motif chemokine receptor 4	Homo sapiens	70-75
29365396-16	2017	But after transfected with a CXCR4-lentivector, the overexpression of CXCR4 was detected and the ratio of apoptosis was significantly lower when co-cultured with MSC which demonstrated that ibrutinib inhibited drug-resistance by inhibiting the expression of CXCR4.	ibrutinib	190-199	C-X-C motif chemokine receptor 4	Homo sapiens	70-75
29365396-21	2017	Conclusion: Ibrutinib targeted the CXCL12/CXCR4 axis, inhibited the expression of CXCR4 and inhibited MSC-mediated drug resistance.	ibrutinib	12-21	C-X-C motif chemokine ligand 12	Homo sapiens	35-41
29365396-21	2017	Conclusion: Ibrutinib targeted the CXCL12/CXCR4 axis, inhibited the expression of CXCR4 and inhibited MSC-mediated drug resistance.	ibrutinib	12-21	C-X-C motif chemokine receptor 4	Homo sapiens	42-47
29365396-21	2017	Conclusion: Ibrutinib targeted the CXCL12/CXCR4 axis, inhibited the expression of CXCR4 and inhibited MSC-mediated drug resistance.	ibrutinib	12-21	C-X-C motif chemokine receptor 4	Homo sapiens	82-87
28922238-7	2017	As mutations leading to the activation of nuclear factor-kappa-B signaling are found in most PCNSLs, with mutations of MYD88 and CD79B particularly, ibrutinib is studied as molecule of great interest and encouraging results have been found in pilot studies.	ibrutinib	149-158	MYD88 innate immune signal transduction adaptor	Homo sapiens	119-124
28922238-7	2017	As mutations leading to the activation of nuclear factor-kappa-B signaling are found in most PCNSLs, with mutations of MYD88 and CD79B particularly, ibrutinib is studied as molecule of great interest and encouraging results have been found in pilot studies.	ibrutinib	149-158	CD79b molecule	Homo sapiens	129-134
28924018-3	2017	Ibrutinib inhibits Bruton tyrosine kinase in B cells and interleukin-2-inducible T-cell kinase in T cells.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	57-94
29082795-7	2017	Because patients with a TP53 deletion/mutation are resistant to chemo-immunotherapy, treatment with the BTK inhibitor ibrutinib is recommended in this setting.	ibrutinib	118-127	tumor protein p53	Homo sapiens	24-28
29082795-7	2017	Because patients with a TP53 deletion/mutation are resistant to chemo-immunotherapy, treatment with the BTK inhibitor ibrutinib is recommended in this setting.	ibrutinib	118-127	Bruton tyrosine kinase	Homo sapiens	104-107
29250930-7	2017	In the relapsed or refractory setting, patients with del(17p) or TP53 aberrations should be offered treatment with a novel agent, such as ibrutinib, idelalisib-rituximab or venetoclax.	ibrutinib	138-147	tumor protein p53	Homo sapiens	65-69
28951258-1	2017	BACKGROUND: Ibrutinib is a Bruton"s tyrosine Kinase (BTK) antagonist that inhibits B cell receptor (BCR) signaling.	ibrutinib	12-21	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	27-51
28951258-1	2017	BACKGROUND: Ibrutinib is a Bruton"s tyrosine Kinase (BTK) antagonist that inhibits B cell receptor (BCR) signaling.	ibrutinib	12-21	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	53-56
28951258-12	2017	In addition, ibrutinib attenuated recall DSA IgG responses to re-sensitization (p&lt;0.05) and reduced CD38+CD138+ plasma cells (p&lt;0.05) in the spleens.	ibrutinib	13-22	CD38 antigen	Mus musculus	103-107
28951258-13	2017	CONCLUSIONS: Ibrutinib is effective in suppressing alloantibody responses through blocking BTK-mediated BCR signaling, leading to reduction of B cells and short-lived plasma cells in the spleens.	ibrutinib	13-22	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	91-94
28705083-2	2017	Nevertheless, only one Btk inhibitor, ibrutinib, has been approved to date, although other compounds are currently being evaluated in clinical trials or in preclinal stages.	ibrutinib	38-47	Bruton tyrosine kinase	Homo sapiens	23-26
28462919-6	2017	CD40L/IL-21-induced proliferation could be inhibited by idelalisib and ibrutinib.	ibrutinib	71-80	CD40 ligand	Homo sapiens	0-5
28462919-6	2017	CD40L/IL-21-induced proliferation could be inhibited by idelalisib and ibrutinib.	ibrutinib	71-80	interleukin 21	Homo sapiens	6-11
29234595-4	2017	Here we present a case of relapsed TP53 mutated CLL treated with ibrutinib as a bridge to alloHCT, discussing risks and benefits of different treatment options in a "real life" situation.	ibrutinib	65-74	tumor protein p53	Homo sapiens	35-39
29296874-2	2017	Introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib has markedly improved MCL therapy outcome, but drug resistance remains a challenge.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	20-42
29296874-2	2017	Introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib has markedly improved MCL therapy outcome, but drug resistance remains a challenge.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	44-47
29296874-7	2017	However, inhibition of the BCR pathway by targeted drugs such as ibrutinib can impair ROR1 expression and consequently ROR1-targeted treatments, underscoring the importance of inhibiting both pathways to augment cancer cell killing.	ibrutinib	65-74	BCR activator of RhoGEF and GTPase	Homo sapiens	27-30
29296874-7	2017	However, inhibition of the BCR pathway by targeted drugs such as ibrutinib can impair ROR1 expression and consequently ROR1-targeted treatments, underscoring the importance of inhibiting both pathways to augment cancer cell killing.	ibrutinib	65-74	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	86-90
29296874-7	2017	However, inhibition of the BCR pathway by targeted drugs such as ibrutinib can impair ROR1 expression and consequently ROR1-targeted treatments, underscoring the importance of inhibiting both pathways to augment cancer cell killing.	ibrutinib	65-74	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	119-123
28295729-3	2017	Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenstrom"s macroglobulinemia; and idelalisib, a PI3Kdelta inhibitor, for the treatment of CLL and follicular lymphoma.	ibrutinib	55-64	Bruton tyrosine kinase	Homo sapiens	68-71
29100012-7	2017	Inhibiting BMX with ibrutinib selectively targeted neoplastic pericytes and disrupted the BTB, but not the BBB, thereby increasing drug effusion into established tumors and enhancing the chemotherapeutic efficacy of drugs with poor BTB penetration.	ibrutinib	20-29	BMX non-receptor tyrosine kinase	Homo sapiens	11-14
28328081-7	2017	Dasatinib and ibrutinib were also found to counteract anti-IgE-induced and allergen-induced upregulation of CD13, CD63, CD164, and CD203c on basophils, whereas AVL-292 and CNX-774 showed no significant effects.	ibrutinib	14-23	alanyl aminopeptidase, membrane	Homo sapiens	108-112
28328081-7	2017	Dasatinib and ibrutinib were also found to counteract anti-IgE-induced and allergen-induced upregulation of CD13, CD63, CD164, and CD203c on basophils, whereas AVL-292 and CNX-774 showed no significant effects.	ibrutinib	14-23	CD63 molecule	Homo sapiens	114-118
28328081-7	2017	Dasatinib and ibrutinib were also found to counteract anti-IgE-induced and allergen-induced upregulation of CD13, CD63, CD164, and CD203c on basophils, whereas AVL-292 and CNX-774 showed no significant effects.	ibrutinib	14-23	CD164 molecule	Homo sapiens	120-125
28328081-7	2017	Dasatinib and ibrutinib were also found to counteract anti-IgE-induced and allergen-induced upregulation of CD13, CD63, CD164, and CD203c on basophils, whereas AVL-292 and CNX-774 showed no significant effects.	ibrutinib	14-23	ectonucleotide pyrophosphatase/phosphodiesterase 3	Homo sapiens	131-137
28798070-0	2017	CXCL13 levels are elevated in patients with Waldenstrom macroglobulinemia, and are predictive of major response to ibrutinib.	ibrutinib	115-124	C-X-C motif chemokine ligand 13	Homo sapiens	0-6
28835384-4	2017	Multiple agents that inhibit the B-cell receptor pathway (e.g., ibrutinib) were found to have synergistic benefit when combined with tazemetostat in both mutant and WT-EZH2 backgrounds of diffuse large B-cell lymphomas (DLBCL).	ibrutinib	64-73	enhancer of zeste 2 polycomb repressive complex 2 subunit	Homo sapiens	168-172
28958786-7	2017	Finally the BTK inhibitor, ibrutinib developed in the LLC has established itself in the management of mantle cell lymphoma and Waldenstrom macroglobulinemia.	ibrutinib	27-36	Bruton tyrosine kinase	Homo sapiens	12-15
28216434-6	2017	RESULTS: Here we show that BTK is a critical regulator of NLRP3 inflammasome activation: pharmacologic (using the US Food and Drug Administration-approved inhibitor ibrutinib) and genetic (in patients with XLA and Btk knockout mice) BTK ablation in primary immune cells led to reduced IL-1beta processing and secretion in response to nigericin and the Staphylococcus aureus toxin leukocidin AB (LukAB).	ibrutinib	165-174	Bruton tyrosine kinase	Homo sapiens	27-30
28216434-6	2017	RESULTS: Here we show that BTK is a critical regulator of NLRP3 inflammasome activation: pharmacologic (using the US Food and Drug Administration-approved inhibitor ibrutinib) and genetic (in patients with XLA and Btk knockout mice) BTK ablation in primary immune cells led to reduced IL-1beta processing and secretion in response to nigericin and the Staphylococcus aureus toxin leukocidin AB (LukAB).	ibrutinib	165-174	NLR family pyrin domain containing 3	Homo sapiens	58-63
28216434-8	2017	S aureus infection control in vivo and IL-1beta release from cells of patients with Muckle-Wells syndrome were impaired by ibrutinib.	ibrutinib	123-132	interleukin 1 beta	Homo sapiens	39-47
28216434-9	2017	Notably, IL-1beta processing and release from immune cells isolated from patients with cancer receiving ibrutinib therapy were reduced.	ibrutinib	104-113	interleukin 1 beta	Homo sapiens	9-17
28482721-4	2017	A potential partner to ibrutinib with a distinct mechanism of action that is likely to lead to deeper responses is the BCL-2 inhibitor venetoclax.	ibrutinib	23-32	BCL2 apoptosis regulator	Homo sapiens	119-124
29263930-9	2017	Moreover, a synergistic reduction in CLL cell viability was observed on co-treatment with CNL and the BTK inhibitor, ibrutinib.	ibrutinib	117-126	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	102-105
28876896-4	2017	We found that Acalabrutinib, CC-292, and Ibrutinib potently and covalently bind TEC family kinases, but only Ibrutinib also potently binds to BLK.	ibrutinib	109-118	BLK proto-oncogene, Src family tyrosine kinase	Homo sapiens	142-145
28876896-5	2017	ZAK was identified as a submicromolar affinity Ibrutinib off-target due to covalent modification of Cys22.	ibrutinib	47-56	mitogen-activated protein kinase kinase kinase 20	Homo sapiens	0-3
28561533-0	2017	Emergence of Bruton"s tyrosine kinase-negative Hodgkin lymphoma during ibrutinib treatment of chronic lymphocytic leukaemia.	ibrutinib	71-80	Bruton tyrosine kinase	Homo sapiens	13-37
28561533-4	2017	We report a case of a 67-year-old female with CLL treated with the novel Bruton"s tyrosine kinase (Btk) inhibitor, ibrutinib, who subsequently presented with intractable fevers.	ibrutinib	115-124	Bruton tyrosine kinase	Homo sapiens	73-97
28561533-4	2017	We report a case of a 67-year-old female with CLL treated with the novel Bruton"s tyrosine kinase (Btk) inhibitor, ibrutinib, who subsequently presented with intractable fevers.	ibrutinib	115-124	Bruton tyrosine kinase	Homo sapiens	99-102
28111464-1	2017	Although the BTK inhibitor ibrutinib has transformed the management of patients with chronic lymphocytic leukemia (CLL), it does not induce substantial apoptosis in vitro, and as such the mechanisms underlying its ability to kill CLL cells are not well understood.	ibrutinib	27-36	Bruton tyrosine kinase	Homo sapiens	13-16
29025288-5	2017	New classes of drugs like kinase inhibitors and BCL-2 inhibitors (ibrutinib, idelalisib and venetoclax) are the treatment of choice in CLL patients with relapsed/refractory disease, with the exception of high risk disease, where the optimal treatment is frontline ibrutinib monotherapy.	ibrutinib	66-75	BCL2 apoptosis regulator	Homo sapiens	48-53
29025288-5	2017	New classes of drugs like kinase inhibitors and BCL-2 inhibitors (ibrutinib, idelalisib and venetoclax) are the treatment of choice in CLL patients with relapsed/refractory disease, with the exception of high risk disease, where the optimal treatment is frontline ibrutinib monotherapy.	ibrutinib	264-273	BCL2 apoptosis regulator	Homo sapiens	48-53
28946903-7	2017	BTK-specific inhibitor ibrutinib effectively inhibits the proliferation, migration and invasion ability of glioma cells.	ibrutinib	23-32	Bruton tyrosine kinase	Homo sapiens	0-3
28580661-6	2017	Treatment of Tg with PCI-32765, a potent Bruton"s tyrosine kinase (BTK) inhibitor for suppressing B cell proliferation and activation, significantly decreased the B cell proportion and IgG2 levels, accompanied by a significantly higher incidence of liver nodules, but had no effects on adenoma and carcinoma.	ibrutinib	21-30	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	41-65
28947822-8	2017	Interestingly, the increase in miR-21 after co-culture was significantly impaired by ibrutinib, indicating that the BCR signaling pathway is involved in its regulation.	ibrutinib	85-94	microRNA 21	Homo sapiens	31-37
28580661-6	2017	Treatment of Tg with PCI-32765, a potent Bruton"s tyrosine kinase (BTK) inhibitor for suppressing B cell proliferation and activation, significantly decreased the B cell proportion and IgG2 levels, accompanied by a significantly higher incidence of liver nodules, but had no effects on adenoma and carcinoma.	ibrutinib	21-30	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	67-70
28619981-0	2017	Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	35-57
28782884-14	2017	Patients with a del(17p) or TP53 mutation can be treated with ibrutinib, venetoclax, or a combination of idelalisib and rituximab.	ibrutinib	62-71	tumor protein p53	Homo sapiens	28-32
28619981-3	2017	We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	73-76
28619981-5	2017	The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism.	ibrutinib	29-38	caspase recruitment domain family member 11	Homo sapiens	103-109
28619981-5	2017	The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism.	ibrutinib	119-128	caspase recruitment domain family member 11	Homo sapiens	103-109
28619981-8	2017	Inhibition of the PI3K isoforms p110alpha/p110delta or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells.Significance: Ibrutinib has substantial activity in patients with relapsed or refractory B-cell lymphoma of the CNS.	ibrutinib	76-85	CD79b molecule	Homo sapiens	110-115
28619981-8	2017	Inhibition of the PI3K isoforms p110alpha/p110delta or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells.Significance: Ibrutinib has substantial activity in patients with relapsed or refractory B-cell lymphoma of the CNS.	ibrutinib	149-158	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	32-41
28619981-8	2017	Inhibition of the PI3K isoforms p110alpha/p110delta or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells.Significance: Ibrutinib has substantial activity in patients with relapsed or refractory B-cell lymphoma of the CNS.	ibrutinib	149-158	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta	Homo sapiens	42-51
28619981-8	2017	Inhibition of the PI3K isoforms p110alpha/p110delta or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells.Significance: Ibrutinib has substantial activity in patients with relapsed or refractory B-cell lymphoma of the CNS.	ibrutinib	149-158	mechanistic target of rapamycin kinase	Homo sapiens	55-59
28619981-8	2017	Inhibition of the PI3K isoforms p110alpha/p110delta or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells.Significance: Ibrutinib has substantial activity in patients with relapsed or refractory B-cell lymphoma of the CNS.	ibrutinib	149-158	CD79b molecule	Homo sapiens	110-115
28619981-10	2017	Combined inhibition of BTK and PI3K/mTOR may augment the ibrutinib response in CD79B-mutant human PCNSLs.	ibrutinib	57-66	Bruton tyrosine kinase	Homo sapiens	23-26
28619981-10	2017	Combined inhibition of BTK and PI3K/mTOR may augment the ibrutinib response in CD79B-mutant human PCNSLs.	ibrutinib	57-66	mechanistic target of rapamycin kinase	Homo sapiens	36-40
28619981-10	2017	Combined inhibition of BTK and PI3K/mTOR may augment the ibrutinib response in CD79B-mutant human PCNSLs.	ibrutinib	57-66	CD79b molecule	Homo sapiens	79-84
28864640-2	2017	Mutations in the B-cell antigen receptor-associated protein CD79B with upregulation of the MTOR pathway were associated with diminished response, but preclinical combination of PIK3CA and PIK3CD inhibitors synergized with ibrutinib to overcome this resistance mechanism, providing opportunity for further targeted therapy of this difficult-to-treat disease.	ibrutinib	222-231	CD79b molecule	Homo sapiens	60-65
28734581-1	2017	Described as a Btk inhibitor, ibrutinib also potently inhibits Bmx and EGFR, two good targets for lung cancer.	ibrutinib	30-39	Bruton tyrosine kinase	Homo sapiens	15-18
28734581-1	2017	Described as a Btk inhibitor, ibrutinib also potently inhibits Bmx and EGFR, two good targets for lung cancer.	ibrutinib	30-39	BMX non-receptor tyrosine kinase	Homo sapiens	63-66
28734581-1	2017	Described as a Btk inhibitor, ibrutinib also potently inhibits Bmx and EGFR, two good targets for lung cancer.	ibrutinib	30-39	epidermal growth factor receptor	Homo sapiens	71-75
28755313-4	2017	We will discuss the landmark clinical trials resulting in the approval of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and the PI3Kdelta inhibitor idelalisib.	ibrutinib	117-126	Bruton tyrosine kinase	Homo sapiens	78-100
28755313-4	2017	We will discuss the landmark clinical trials resulting in the approval of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and the PI3Kdelta inhibitor idelalisib.	ibrutinib	117-126	Bruton tyrosine kinase	Homo sapiens	102-105
28864640-2	2017	Mutations in the B-cell antigen receptor-associated protein CD79B with upregulation of the MTOR pathway were associated with diminished response, but preclinical combination of PIK3CA and PIK3CD inhibitors synergized with ibrutinib to overcome this resistance mechanism, providing opportunity for further targeted therapy of this difficult-to-treat disease.	ibrutinib	222-231	mechanistic target of rapamycin kinase	Homo sapiens	91-95
28864640-2	2017	Mutations in the B-cell antigen receptor-associated protein CD79B with upregulation of the MTOR pathway were associated with diminished response, but preclinical combination of PIK3CA and PIK3CD inhibitors synergized with ibrutinib to overcome this resistance mechanism, providing opportunity for further targeted therapy of this difficult-to-treat disease.	ibrutinib	222-231	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	177-183
28864640-2	2017	Mutations in the B-cell antigen receptor-associated protein CD79B with upregulation of the MTOR pathway were associated with diminished response, but preclinical combination of PIK3CA and PIK3CD inhibitors synergized with ibrutinib to overcome this resistance mechanism, providing opportunity for further targeted therapy of this difficult-to-treat disease.	ibrutinib	222-231	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta	Homo sapiens	188-194
28619845-0	2017	The prohibitin-binding compound fluorizoline induces apoptosis in chronic lymphocytic leukemia cells through the upregulation of NOXA and synergizes with ibrutinib, 5-aminoimidazole-4-carboxamide riboside or venetoclax.	ibrutinib	154-163	prohibitin 1	Homo sapiens	4-14
28810856-3	2017	At the 2017 ASCO Meeting, results of the GENUINE phase III trial showed that, by adding ublituximab, a glycoengineered, anti-CD20 type 1 monoclonal antibody, to ibrutinib, the overall response rate (ORR), complete response rate (CRR), and minimal residual disease (MRD) negativity may be improved in high-risk CLL patients.	ibrutinib	161-170	keratin 20	Homo sapiens	125-129
28056114-15	2017	Ibrutinib is efficacious in patients with relapsed or refractory disease harboring MYD88 L265P mutation.	ibrutinib	0-9	MYD88 innate immune signal transduction adaptor	Homo sapiens	83-88
28710251-10	2017	Deregulation of ZAP-70 using tyrosine kinase inhibitors, gefitinib or ibrutinib, diminishes HA formation and trogocytosis by GA101.	ibrutinib	70-79	zeta chain of T cell receptor associated protein kinase 70	Homo sapiens	16-22
28810856-4	2017	A further way to improve the results obtained with Bruton"s tyrosine kinase (BTK) inhibitors is the parallel use of ibrutinib with chimeric antigen receptor (CAR) T-cell therapy.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	51-75
28810856-4	2017	A further way to improve the results obtained with Bruton"s tyrosine kinase (BTK) inhibitors is the parallel use of ibrutinib with chimeric antigen receptor (CAR) T-cell therapy.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	77-80
28368423-7	2017	Notably, Myc-overexpressing B cells maintained elevated BCR signaling despite treatment with ibrutinib, a Bruton"s tyrosine kinase inhibitor.	ibrutinib	93-102	myelocytomatosis oncogene	Mus musculus	9-12
28368423-8	2017	Furthermore, PI3K/Akt pathway signaling was also increased in Emu-myc B cells, and this increase was partially suppressed with ibrutinib.	ibrutinib	127-136	thymoma viral proto-oncogene 1	Mus musculus	18-21
28368423-8	2017	Furthermore, PI3K/Akt pathway signaling was also increased in Emu-myc B cells, and this increase was partially suppressed with ibrutinib.	ibrutinib	127-136	myelocytomatosis oncogene	Mus musculus	66-69
28368423-9	2017	In addition, experiments with Btk-null B cells revealed off-target effects of ibrutinib on BCR signaling.	ibrutinib	78-87	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	30-33
28714866-11	2017	CONCLUSIONS: Ibrutinib treatment increased the in vivo persistence of activated T cells, decreased the Treg/CD4+ T cell ratio, and diminished the immune-suppressive properties of CLL cells through BTK-dependent and -independent mechanisms.	ibrutinib	13-22	Bruton tyrosine kinase	Homo sapiens	197-200
28348046-5	2017	In the acquired ibrutinib-resistant PDXs, PLC-gamma2, p65, and Src were downregulated; however, a PI3K signaling pathway member was upregulated.	ibrutinib	16-25	phospholipase C gamma 2	Homo sapiens	42-52
28348046-5	2017	In the acquired ibrutinib-resistant PDXs, PLC-gamma2, p65, and Src were downregulated; however, a PI3K signaling pathway member was upregulated.	ibrutinib	16-25	RELA proto-oncogene, NF-kB subunit	Homo sapiens	54-57
28348046-5	2017	In the acquired ibrutinib-resistant PDXs, PLC-gamma2, p65, and Src were downregulated; however, a PI3K signaling pathway member was upregulated.	ibrutinib	16-25	SRC proto-oncogene, non-receptor tyrosine kinase	Homo sapiens	63-66
28617062-5	2017	Expert commentary: Novel agents such as the BTK inhibitor ibrutinib has shown to be safe and highly effective in the treatment of WM.	ibrutinib	58-67	Bruton tyrosine kinase	Homo sapiens	44-47
28714866-1	2017	BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton"s tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	84-108
28714866-1	2017	BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton"s tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	110-113
28714866-1	2017	BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton"s tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK).	ibrutinib	12-21	IL2 inducible T cell kinase	Homo sapiens	119-147
28751718-3	2017	Both del(17p) and del(11q) are also associated with inferior outcome to the novel targeted agents, such as the BTK inhibitor ibrutinib.	ibrutinib	125-134	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	111-114
28714866-1	2017	BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton"s tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK).	ibrutinib	12-21	IL2 inducible T cell kinase	Homo sapiens	149-152
28938632-6	2017	In the in vitro assays, the combination of Ibrutinib+GSI exhibited enhanced cytotoxicity on B-CLL cells also in the presence of stroma and it was coupled to the down-regulation of the stroma-activated NOTCH1 and c-MYC pathways.	ibrutinib	43-52	notch receptor 1	Homo sapiens	201-207
28938632-6	2017	In the in vitro assays, the combination of Ibrutinib+GSI exhibited enhanced cytotoxicity on B-CLL cells also in the presence of stroma and it was coupled to the down-regulation of the stroma-activated NOTCH1 and c-MYC pathways.	ibrutinib	43-52	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	212-217
28716053-0	2017	Ibrutinib, a Bruton"s tyrosine kinase inhibitor, exhibits antitumoral activity and induces autophagy in glioblastoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-37
28716053-2	2017	Ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor, is a novel anticancer drug used for treating several types of cancers.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-37
28716053-2	2017	Ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor, is a novel anticancer drug used for treating several types of cancers.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	39-42
28716053-13	2017	Overexpression of the active Akt protein decreased ibrutinib-induced autophagy, while inhibiting Akt by LY294002 treatment enhanced ibrutinib-induced autophagy.	ibrutinib	51-60	AKT serine/threonine kinase 1	Homo sapiens	29-32
28716053-13	2017	Overexpression of the active Akt protein decreased ibrutinib-induced autophagy, while inhibiting Akt by LY294002 treatment enhanced ibrutinib-induced autophagy.	ibrutinib	132-141	AKT serine/threonine kinase 1	Homo sapiens	97-100
28716053-14	2017	Specific inhibition of autophagy by 3-methyladenine (3MA) or Atg7 targeting with small interfering RNA (si-Atg7) enhanced the anti-GBM effect of ibrutinib in vitro and in vivo.	ibrutinib	145-154	autophagy related 7	Homo sapiens	61-65
28716053-14	2017	Specific inhibition of autophagy by 3-methyladenine (3MA) or Atg7 targeting with small interfering RNA (si-Atg7) enhanced the anti-GBM effect of ibrutinib in vitro and in vivo.	ibrutinib	145-154	autophagy related 7	Homo sapiens	107-111
28716053-15	2017	CONCLUSIONS: Our results indicate that ibrutinib exerts a profound antitumor effect and induces autophagy through Akt/mTOR signaling pathway in GBM cells.	ibrutinib	39-48	AKT serine/threonine kinase 1	Homo sapiens	114-117
28716053-15	2017	CONCLUSIONS: Our results indicate that ibrutinib exerts a profound antitumor effect and induces autophagy through Akt/mTOR signaling pathway in GBM cells.	ibrutinib	39-48	mechanistic target of rapamycin kinase	Homo sapiens	118-122
28034907-1	2017	Purpose: Ibrutinib inhibits Bruton tyrosine kinase (BTK) by irreversibly binding to the Cys-481 residue in the enzyme.	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	28-50
28034907-1	2017	Purpose: Ibrutinib inhibits Bruton tyrosine kinase (BTK) by irreversibly binding to the Cys-481 residue in the enzyme.	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	52-55
28034907-2	2017	However, ibrutinib also inhibits several other enzymes that contain cysteine residues homologous to Cys-481 in BTK.	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	111-114
28495793-3	2017	This suggests that targeting USP7 may have therapeutic potential even in tumors with defective p53 or ibrutinib resistance.	ibrutinib	102-111	ubiquitin specific peptidase 7	Mus musculus	29-33
28536906-4	2017	The biological function of BTK in several B-cell lymphoid malignancies has led to the development of the oral BTK inhibitor ibrutinib.	ibrutinib	124-133	Bruton tyrosine kinase	Homo sapiens	27-30
28342031-2	2017	Ibrutinib is a BTK inhibitor that has shown excellent efficacy in treatment-naive, heavily pre-treated, and high-risk CLL/SLL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	15-18
28342031-2	2017	Ibrutinib is a BTK inhibitor that has shown excellent efficacy in treatment-naive, heavily pre-treated, and high-risk CLL/SLL.	ibrutinib	0-9	solute carrier family 35 member B2	Homo sapiens	122-125
28342031-6	2017	Several promising novel agents are currently in early phases of development for overcoming ibrutinib resistance in CLL/SLL.	ibrutinib	91-100	solute carrier family 35 member B2	Homo sapiens	119-122
28419476-8	2017	Reduced Cortactin expression and phosphorylation were also detected both in vivo and in vitro after treatment with Ibrutinib, a Btk inhibitor.	ibrutinib	115-124	cortactin	Homo sapiens	8-17
28419476-8	2017	Reduced Cortactin expression and phosphorylation were also detected both in vivo and in vitro after treatment with Ibrutinib, a Btk inhibitor.	ibrutinib	115-124	Bruton tyrosine kinase	Homo sapiens	128-131
28641100-4	2017	Ibrutinib (PCI-32765) is an orally available small molecule that acts as an inhibitor of the BTK and is approved for the treatment of patients with some hematological malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	93-96
28641100-6	2017	In this sense, ibrutinib has the ability to revert polarization of TCD4+ to Th1 lymphocytes to increase the cytotoxic ability of T CD8+ and to regulate tumor-induced immune tolerance by acting over tumor infiltrating cells activity and immunosuppressive cytokines release.	ibrutinib	15-24	negative elongation factor complex member C/D	Homo sapiens	76-79
28641100-7	2017	Furthermore, based on its molecular activity and safety, ibrutinib has been considered as a partner for treatment combination with PI3K/AKT/mTOR inhibitors or with immune-checkpoint inhibitors, inhibiting immunosuppressive signals from the tumor microenvironment, and overcoming the immune resistance to current anti-PD1/PDL1 immunotherapeutic drugs by the CXCR4/CXCL2 pathway regulation.	ibrutinib	57-66	AKT serine/threonine kinase 1	Homo sapiens	136-139
28641100-7	2017	Furthermore, based on its molecular activity and safety, ibrutinib has been considered as a partner for treatment combination with PI3K/AKT/mTOR inhibitors or with immune-checkpoint inhibitors, inhibiting immunosuppressive signals from the tumor microenvironment, and overcoming the immune resistance to current anti-PD1/PDL1 immunotherapeutic drugs by the CXCR4/CXCL2 pathway regulation.	ibrutinib	57-66	mechanistic target of rapamycin kinase	Homo sapiens	140-144
28641100-7	2017	Furthermore, based on its molecular activity and safety, ibrutinib has been considered as a partner for treatment combination with PI3K/AKT/mTOR inhibitors or with immune-checkpoint inhibitors, inhibiting immunosuppressive signals from the tumor microenvironment, and overcoming the immune resistance to current anti-PD1/PDL1 immunotherapeutic drugs by the CXCR4/CXCL2 pathway regulation.	ibrutinib	57-66	programmed cell death 1	Homo sapiens	317-320
28641100-7	2017	Furthermore, based on its molecular activity and safety, ibrutinib has been considered as a partner for treatment combination with PI3K/AKT/mTOR inhibitors or with immune-checkpoint inhibitors, inhibiting immunosuppressive signals from the tumor microenvironment, and overcoming the immune resistance to current anti-PD1/PDL1 immunotherapeutic drugs by the CXCR4/CXCL2 pathway regulation.	ibrutinib	57-66	CD274 molecule	Homo sapiens	321-325
28641100-7	2017	Furthermore, based on its molecular activity and safety, ibrutinib has been considered as a partner for treatment combination with PI3K/AKT/mTOR inhibitors or with immune-checkpoint inhibitors, inhibiting immunosuppressive signals from the tumor microenvironment, and overcoming the immune resistance to current anti-PD1/PDL1 immunotherapeutic drugs by the CXCR4/CXCL2 pathway regulation.	ibrutinib	57-66	C-X-C motif chemokine receptor 4	Homo sapiens	357-362
28641100-7	2017	Furthermore, based on its molecular activity and safety, ibrutinib has been considered as a partner for treatment combination with PI3K/AKT/mTOR inhibitors or with immune-checkpoint inhibitors, inhibiting immunosuppressive signals from the tumor microenvironment, and overcoming the immune resistance to current anti-PD1/PDL1 immunotherapeutic drugs by the CXCR4/CXCL2 pathway regulation.	ibrutinib	57-66	C-X-C motif chemokine ligand 2	Homo sapiens	363-368
28760303-0	2017	Analysis of Efficacy and Tolerability of Bruton Tyrosine Kinase Inhibitor Ibrutinib in Various B-cell Malignancies in the General Community: A Single-center Experience.	ibrutinib	74-83	Bruton tyrosine kinase	Homo sapiens	41-63
28760303-1	2017	BACKGROUND: Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B-cell malignancies.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	52-74
28760303-1	2017	BACKGROUND: Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B-cell malignancies.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	76-79
28536906-4	2017	The biological function of BTK in several B-cell lymphoid malignancies has led to the development of the oral BTK inhibitor ibrutinib.	ibrutinib	124-133	Bruton tyrosine kinase	Homo sapiens	110-113
28536906-10	2017	Studies evaluating other potential indications for BTK inhibition are ongoing, including in post-allogeneic hematopoietic stem cell transplant patients for whom ibrutinib may be effective in modulating graft-versus-host disease.	ibrutinib	161-170	Bruton tyrosine kinase	Homo sapiens	51-54
28536906-11	2017	Combination trials of ibrutinib with venetoclax, a Bcl-2 inhibitor, are underway and are supported by sound preclinical rationale.	ibrutinib	22-31	BCL2 apoptosis regulator	Homo sapiens	51-56
28428442-2	2017	Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	30-33
28341730-0	2017	Combination of ibrutinib and chemotherapy produced a durable remission in multiply relapsed diffuse large B-cell lymphoma leg type with mutant MYD88 and wildtype CD79.	ibrutinib	15-24	MYD88 innate immune signal transduction adaptor	Homo sapiens	143-148
28428442-4	2017	Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor.	ibrutinib	0-9	BCL2 apoptosis regulator	Homo sapiens	42-46
28428442-4	2017	Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor.	ibrutinib	0-9	BCL2 apoptosis regulator	Homo sapiens	103-108
28428442-5	2017	Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression.	ibrutinib	90-99	BCL2 apoptosis regulator	Homo sapiens	111-115
28424405-0	2017	The Bruton"s tyrosine kinase inhibitor ibrutinib exerts immunomodulatory effects through regulation of tumor-infiltrating macrophages.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	4-28
28366935-0	2017	PLCG2 C2 domain mutations co-occur with BTK and PLCG2 resistance mutations in chronic lymphocytic leukemia undergoing ibrutinib treatment.	ibrutinib	118-127	phospholipase C gamma 2	Homo sapiens	0-5
28366935-0	2017	PLCG2 C2 domain mutations co-occur with BTK and PLCG2 resistance mutations in chronic lymphocytic leukemia undergoing ibrutinib treatment.	ibrutinib	118-127	phospholipase C gamma 2	Homo sapiens	48-53
27993968-0	2017	Mechanisms of Acquired Drug Resistance to the HDAC6 Selective Inhibitor Ricolinostat Reveals Rational Drug-Drug Combination with Ibrutinib.	ibrutinib	129-138	histone deacetylase 6	Homo sapiens	46-51
28424405-1	2017	The Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib has demonstrated promising efficacy in a variety of hematologic malignancies.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
28424405-1	2017	The Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib has demonstrated promising efficacy in a variety of hematologic malignancies.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
27904138-0	2017	Cirmtuzumab inhibits Wnt5a-induced Rac1 activation in chronic lymphocytic leukemia treated with ibrutinib.	ibrutinib	96-105	Wnt family member 5A	Homo sapiens	21-26
28552326-2	2017	demonstrate that the combination of temozolomide, etoposide, doxorubicin, dexamethasone, rituximab, and the Bruton tyrosine kinase (BTK) inhibitor ibrutinib induced frequent responses in patients with primary central nervous system lymphoma but was associated with significant toxicity, including pulmonary and cerebral aspergillosis infections.	ibrutinib	147-156	Bruton tyrosine kinase	Homo sapiens	108-130
28552326-2	2017	demonstrate that the combination of temozolomide, etoposide, doxorubicin, dexamethasone, rituximab, and the Bruton tyrosine kinase (BTK) inhibitor ibrutinib induced frequent responses in patients with primary central nervous system lymphoma but was associated with significant toxicity, including pulmonary and cerebral aspergillosis infections.	ibrutinib	147-156	Bruton tyrosine kinase	Homo sapiens	132-135
28552327-2	2017	Ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-37
28552327-2	2017	Ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	39-42
28552327-2	2017	Ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88.	ibrutinib	0-9	CD79b molecule	Homo sapiens	157-162
28552327-2	2017	Ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88.	ibrutinib	0-9	MYD88 innate immune signal transduction adaptor	Homo sapiens	167-172
27820970-1	2017	Due to Cytochrome P450 3A (CYP3A) metabolism, clinical trials of ibrutinib-treated chronic lymphocytic leukemia (CLL) patients prohibited concurrent medications metabolized by CYP3A.	ibrutinib	65-74	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	7-25
27820970-1	2017	Due to Cytochrome P450 3A (CYP3A) metabolism, clinical trials of ibrutinib-treated chronic lymphocytic leukemia (CLL) patients prohibited concurrent medications metabolized by CYP3A.	ibrutinib	65-74	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	27-32
27820970-1	2017	Due to Cytochrome P450 3A (CYP3A) metabolism, clinical trials of ibrutinib-treated chronic lymphocytic leukemia (CLL) patients prohibited concurrent medications metabolized by CYP3A.	ibrutinib	65-74	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	176-181
27904138-0	2017	Cirmtuzumab inhibits Wnt5a-induced Rac1 activation in chronic lymphocytic leukemia treated with ibrutinib.	ibrutinib	96-105	Rac family small GTPase 1	Homo sapiens	35-39
27904138-2	2017	This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton"s tyrosine kinase (BTK) that can block BCR-signaling.	ibrutinib	53-62	Bruton tyrosine kinase	Homo sapiens	80-104
27904138-2	2017	This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton"s tyrosine kinase (BTK) that can block BCR-signaling.	ibrutinib	53-62	Bruton tyrosine kinase	Homo sapiens	106-109
27904138-5	2017	In this study, we found that CLL cells of patients treated with ibrutinib had activated Rac1.	ibrutinib	64-73	Rac family small GTPase 1	Homo sapiens	88-92
27904138-6	2017	Moreover, Wnt5a could induce Rac1 activation and enhance proliferation of CLL cells treated with ibrutinib at concentrations that were effective in completely inhibiting BTK and BCR-signaling.	ibrutinib	97-106	Wnt family member 5A	Homo sapiens	10-15
27904138-6	2017	Moreover, Wnt5a could induce Rac1 activation and enhance proliferation of CLL cells treated with ibrutinib at concentrations that were effective in completely inhibiting BTK and BCR-signaling.	ibrutinib	97-106	Rac family small GTPase 1	Homo sapiens	29-33
27904138-6	2017	Moreover, Wnt5a could induce Rac1 activation and enhance proliferation of CLL cells treated with ibrutinib at concentrations that were effective in completely inhibiting BTK and BCR-signaling.	ibrutinib	97-106	Bruton tyrosine kinase	Homo sapiens	170-173
27904138-9	2017	This study indicates that cirmtuzumab may enhance the activity of ibrutinib in the treatment of patients with CLL or other ROR1+ B-cell malignancies.	ibrutinib	66-75	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	123-127
28265007-0	2017	The BTK Inhibitor Ibrutinib (PCI-32765) Overcomes Paclitaxel Resistance in ABCB1- and ABCC10-Overexpressing Cells and Tumors.	ibrutinib	18-27	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	75-80
28265007-0	2017	The BTK Inhibitor Ibrutinib (PCI-32765) Overcomes Paclitaxel Resistance in ABCB1- and ABCC10-Overexpressing Cells and Tumors.	ibrutinib	18-27	ATP-binding cassette, sub-family C (CFTR/MRP), member 10	Mus musculus	86-92
28265007-4	2017	Here, we demonstrated that the Bruton tyrosine kinase inhibitor, ibrutinib, significantly enhanced the antitumor activity of paclitaxel by antagonizing the efflux function of ABCB1 and ABCC10 in cells overexpressing these transporters.	ibrutinib	65-74	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	175-180
28265007-4	2017	Here, we demonstrated that the Bruton tyrosine kinase inhibitor, ibrutinib, significantly enhanced the antitumor activity of paclitaxel by antagonizing the efflux function of ABCB1 and ABCC10 in cells overexpressing these transporters.	ibrutinib	65-74	ATP-binding cassette, sub-family C (CFTR/MRP), member 10	Mus musculus	185-191
28265007-6	2017	However, the ATPase activity of ABCB1 was significantly stimulated by treatment with ibrutinib.	ibrutinib	85-94	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	32-37
28265007-7	2017	Molecular docking analysis suggested the binding conformation of ibrutinib within the large cavity of the transmembrane region of ABCB1.	ibrutinib	65-74	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	130-135
28548645-0	2017	Waldenstrom macroglobulinemia cells devoid of BTKC481S or CXCR4WHIM-like mutations acquire resistance to ibrutinib through upregulation of Bcl-2 and AKT resulting in vulnerability towards venetoclax or MK2206 treatment.	ibrutinib	105-114	C-X-C motif chemokine receptor 4	Homo sapiens	58-63
28265007-8	2017	Importantly, ibrutinib could effectively enhance paclitaxel-induced inhibition on the growth of ABCB1- and ABCC10-overexpressing tumors in nude athymic mice.	ibrutinib	13-22	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	96-101
28265007-8	2017	Importantly, ibrutinib could effectively enhance paclitaxel-induced inhibition on the growth of ABCB1- and ABCC10-overexpressing tumors in nude athymic mice.	ibrutinib	13-22	ATP-binding cassette, sub-family C (CFTR/MRP), member 10	Mus musculus	107-113
28265007-9	2017	These results demonstrate that the combination of ibrutinib and paclitaxel can effectively antagonize ABCB1- or ABCC10-mediated paclitaxel resistance that could be of great clinical interest.	ibrutinib	50-59	ATP-binding cassette, sub-family B (MDR/TAP), member 1B	Mus musculus	102-107
28265007-9	2017	These results demonstrate that the combination of ibrutinib and paclitaxel can effectively antagonize ABCB1- or ABCC10-mediated paclitaxel resistance that could be of great clinical interest.	ibrutinib	50-59	ATP-binding cassette, sub-family C (CFTR/MRP), member 10	Mus musculus	112-118
28641630-0	2017	[SDF-1alpha/CXCR4 Mediated Drug Resistance Can be Reversed by Ibrutinib in Acute Lymphoblastic Leukemia].	ibrutinib	62-71	C-X-C motif chemokine receptor 4	Homo sapiens	12-17
28641630-1	2017	OBJECTIVE: To explore the effect of Ibrutinib on the chemoresistance mediated by SDF-1alpha/CXCR4 axis in ALL cells.	ibrutinib	36-45	C-X-C motif chemokine receptor 4	Homo sapiens	92-97
28641630-3	2017	RESULTS: Ibrutinib enhanced the apoptosis induced by adriamycin(ADR) (17.100+-4.3% to 28.133+-3.16%); Ibrutinib inhibited the phosphorylation of CXCR4 induced by SDF-1alpha and with concentration- and time- dependent manner (r24h=-0.99659, r48h=-0.99764, r=-0.99980).	ibrutinib	9-18	C-X-C motif chemokine receptor 4	Homo sapiens	145-150
28641630-3	2017	RESULTS: Ibrutinib enhanced the apoptosis induced by adriamycin(ADR) (17.100+-4.3% to 28.133+-3.16%); Ibrutinib inhibited the phosphorylation of CXCR4 induced by SDF-1alpha and with concentration- and time- dependent manner (r24h=-0.99659, r48h=-0.99764, r=-0.99980).	ibrutinib	102-111	C-X-C motif chemokine receptor 4	Homo sapiens	145-150
28641630-4	2017	Ibrutinib inhibited the expression and activity of CXCR4 downstream signaling molecules pERK and BCL-xL.	ibrutinib	0-9	C-X-C motif chemokine receptor 4	Homo sapiens	51-56
28641630-4	2017	Ibrutinib inhibited the expression and activity of CXCR4 downstream signaling molecules pERK and BCL-xL.	ibrutinib	0-9	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	88-92
28641630-4	2017	Ibrutinib inhibited the expression and activity of CXCR4 downstream signaling molecules pERK and BCL-xL.	ibrutinib	0-9	BCL2 like 1	Homo sapiens	97-103
28641630-5	2017	CONCLUSION: Ibrutinib can enhance the sensitivity of SUP-B15 to ADR, reverse SDF-1alpha/CXCR4-mediated chemoresistance in Ph+ acute lymphoblastic leukemia cells.	ibrutinib	12-21	C-X-C motif chemokine receptor 4	Homo sapiens	88-93
28641630-6	2017	This mechanism of ibrutinib may be assosiated with inhibiting CXCR4/ERK/BCL-xL.	ibrutinib	18-27	C-X-C motif chemokine receptor 4	Homo sapiens	62-67
28641630-6	2017	This mechanism of ibrutinib may be assosiated with inhibiting CXCR4/ERK/BCL-xL.	ibrutinib	18-27	mitogen-activated protein kinase 1	Homo sapiens	68-71
28641630-6	2017	This mechanism of ibrutinib may be assosiated with inhibiting CXCR4/ERK/BCL-xL.	ibrutinib	18-27	BCL2 like 1	Homo sapiens	72-78
28548645-0	2017	Waldenstrom macroglobulinemia cells devoid of BTKC481S or CXCR4WHIM-like mutations acquire resistance to ibrutinib through upregulation of Bcl-2 and AKT resulting in vulnerability towards venetoclax or MK2206 treatment.	ibrutinib	105-114	BCL2 apoptosis regulator	Homo sapiens	139-144
28548645-0	2017	Waldenstrom macroglobulinemia cells devoid of BTKC481S or CXCR4WHIM-like mutations acquire resistance to ibrutinib through upregulation of Bcl-2 and AKT resulting in vulnerability towards venetoclax or MK2206 treatment.	ibrutinib	105-114	AKT serine/threonine kinase 1	Homo sapiens	149-152
28548645-7	2017	Our findings demonstrate that induction of ibrutinib resistance in WM cells can arise independent of BTKC481S and CXCR4WHIM-like mutations and sustained pressure from ibrutinib appears to activate compensatory AKT signaling as well as reshuffling of Bcl-2 family proteins for maintenance of cell survival.	ibrutinib	43-52	BCL2 apoptosis regulator	Homo sapiens	250-255
28548645-7	2017	Our findings demonstrate that induction of ibrutinib resistance in WM cells can arise independent of BTKC481S and CXCR4WHIM-like mutations and sustained pressure from ibrutinib appears to activate compensatory AKT signaling as well as reshuffling of Bcl-2 family proteins for maintenance of cell survival.	ibrutinib	167-176	AKT serine/threonine kinase 1	Homo sapiens	210-213
29069762-8	2017	Treatment of cell line-engrafted Rag1-/- mice with ibrutinib was associated with transient lymphocytosis, reduced splenomegaly and increased overall survival.	ibrutinib	51-60	recombination activating 1	Mus musculus	33-37
29069762-7	2017	Treatment of the cell lines with small molecule inhibitors specific for Btk (ibrutinib) or PI3K (idelalisib), which is upstream of Akt, resulted in reduced viability, proliferation and fibronectin-dependent cell adhesion.	ibrutinib	77-86	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	72-75
28235842-1	2017	Ibrutinib produces high response rates and durable remissions in Waldenstrom macroglobulinemia (WM) that are impacted by MYD88 and CXCR4WHIM mutations.	ibrutinib	0-9	MYD88 innate immune signal transduction adaptor	Homo sapiens	121-126
29069762-7	2017	Treatment of the cell lines with small molecule inhibitors specific for Btk (ibrutinib) or PI3K (idelalisib), which is upstream of Akt, resulted in reduced viability, proliferation and fibronectin-dependent cell adhesion.	ibrutinib	77-86	thymoma viral proto-oncogene 1	Mus musculus	131-134
29069762-7	2017	Treatment of the cell lines with small molecule inhibitors specific for Btk (ibrutinib) or PI3K (idelalisib), which is upstream of Akt, resulted in reduced viability, proliferation and fibronectin-dependent cell adhesion.	ibrutinib	77-86	fibronectin 1	Mus musculus	185-196
29113297-7	2017	Results showed that overexpression of ROR1-AS1 lncRNA promoted growth of MCL cells while decreased sensitivity to the treatment with drugs ibrutinib and dexamethasone.	ibrutinib	139-148	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	38-42
29113297-7	2017	Results showed that overexpression of ROR1-AS1 lncRNA promoted growth of MCL cells while decreased sensitivity to the treatment with drugs ibrutinib and dexamethasone.	ibrutinib	139-148	prostaglandin D2 receptor	Homo sapiens	43-46
28373262-1	2017	Ibrutinib, an oral inhibitor of Bruton"s tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	32-56
28373262-1	2017	Ibrutinib, an oral inhibitor of Bruton"s tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	58-61
28373262-1	2017	Ibrutinib, an oral inhibitor of Bruton"s tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	104-107
28235842-1	2017	Ibrutinib produces high response rates and durable remissions in Waldenstrom macroglobulinemia (WM) that are impacted by MYD88 and CXCR4WHIM mutations.	ibrutinib	0-9	C-X-C motif chemokine receptor 4	Homo sapiens	131-136
28146266-6	2017	The CD22-targeted immunoconjugate moxetumomab pasudotox and BTK inhibitor ibrutinib also achieve responses in relapsed and refractory patients.	ibrutinib	74-83	CD22 molecule	Homo sapiens	4-8
27797975-1	2017	Background: Ibrutinib is an active therapy with an acceptable safety profile for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del17p or with TP53 mutations.	ibrutinib	12-21	tumor protein p53	Homo sapiens	180-184
28146266-6	2017	The CD22-targeted immunoconjugate moxetumomab pasudotox and BTK inhibitor ibrutinib also achieve responses in relapsed and refractory patients.	ibrutinib	74-83	Bruton tyrosine kinase	Homo sapiens	60-63
28182323-1	2017	Ibrutinib is an irreversible inhibitor of Bruton"s tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	42-66
28163195-3	2017	Notably, the CD80high MZ B cells were more sensitive to ibrutinib, a Bruton"s tyrosine kinase inhibitor, than CD80low MZ or follicular B cells and their transient depletion via intravenous injection of ibrutinib significantly delayed the induction of collagen-induced arthritis (CIA).	ibrutinib	56-65	CD80 antigen	Mus musculus	13-17
28163195-3	2017	Notably, the CD80high MZ B cells were more sensitive to ibrutinib, a Bruton"s tyrosine kinase inhibitor, than CD80low MZ or follicular B cells and their transient depletion via intravenous injection of ibrutinib significantly delayed the induction of collagen-induced arthritis (CIA).	ibrutinib	202-211	CD80 antigen	Mus musculus	13-17
28418267-1	2017	Purpose Therapeutic targeting of Bruton tyrosine kinase (BTK) with ibrutinib in chronic lymphocytic leukemia has led to a paradigm shift in therapy, and relapse has been uncommon with current follow-up.	ibrutinib	67-76	Bruton tyrosine kinase	Homo sapiens	33-55
28418267-1	2017	Purpose Therapeutic targeting of Bruton tyrosine kinase (BTK) with ibrutinib in chronic lymphocytic leukemia has led to a paradigm shift in therapy, and relapse has been uncommon with current follow-up.	ibrutinib	67-76	Bruton tyrosine kinase	Homo sapiens	57-60
27909342-1	2017	Bleeding because of impaired platelet function is a major side effect of the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib.	ibrutinib	118-127	Bruton tyrosine kinase	Homo sapiens	77-101
27909342-1	2017	Bleeding because of impaired platelet function is a major side effect of the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib.	ibrutinib	118-127	Bruton tyrosine kinase	Homo sapiens	103-106
28182323-1	2017	Ibrutinib is an irreversible inhibitor of Bruton"s tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	68-71
28294689-12	2017	Ibrutinib is active in patients with WM and is affected by MYD88 and CXCR4 mutation status.	ibrutinib	0-9	MYD88 innate immune signal transduction adaptor	Homo sapiens	59-64
28416797-3	2017	We demonstrate that MCL cells develop ibrutinib resistance through evolutionary processes driven by dynamic feedback between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing the effect of ibrutinib and reciprocal activation of PI3K-AKT-mTOR and integrin-beta1 signalling.	ibrutinib	38-47	mechanistic target of rapamycin kinase	Homo sapiens	258-262
28416797-3	2017	We demonstrate that MCL cells develop ibrutinib resistance through evolutionary processes driven by dynamic feedback between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing the effect of ibrutinib and reciprocal activation of PI3K-AKT-mTOR and integrin-beta1 signalling.	ibrutinib	38-47	integrin subunit beta 1	Homo sapiens	267-281
28275136-6	2017	The increased S6 kinase phosphorylation in Tec-deficient B cells was dependent on Btk kinase activity, as ibrutinib treatment restored pS6 to wild-type levels, although Btk protein and phosphorylation levels were comparable to controls.	ibrutinib	106-115	tec protein tyrosine kinase	Mus musculus	43-46
28275136-6	2017	The increased S6 kinase phosphorylation in Tec-deficient B cells was dependent on Btk kinase activity, as ibrutinib treatment restored pS6 to wild-type levels, although Btk protein and phosphorylation levels were comparable to controls.	ibrutinib	106-115	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	82-85
28282122-1	2017	On the basis of Ibrutinib"s core pharmacophore, which was moderately active to EGFR T790M mutant, we discovered novel epidermal growth factor receptor (EGFR) inhibitor compound 19 (CHMFL-EGFR-202), which potently inhibited EGFR primary mutants (L858R, del19) and drug-resistant mutant L858R/T790M.	ibrutinib	16-25	epidermal growth factor receptor	Homo sapiens	79-83
28282122-1	2017	On the basis of Ibrutinib"s core pharmacophore, which was moderately active to EGFR T790M mutant, we discovered novel epidermal growth factor receptor (EGFR) inhibitor compound 19 (CHMFL-EGFR-202), which potently inhibited EGFR primary mutants (L858R, del19) and drug-resistant mutant L858R/T790M.	ibrutinib	16-25	epidermal growth factor receptor	Homo sapiens	118-150
28282122-1	2017	On the basis of Ibrutinib"s core pharmacophore, which was moderately active to EGFR T790M mutant, we discovered novel epidermal growth factor receptor (EGFR) inhibitor compound 19 (CHMFL-EGFR-202), which potently inhibited EGFR primary mutants (L858R, del19) and drug-resistant mutant L858R/T790M.	ibrutinib	16-25	epidermal growth factor receptor	Homo sapiens	152-156
28282122-1	2017	On the basis of Ibrutinib"s core pharmacophore, which was moderately active to EGFR T790M mutant, we discovered novel epidermal growth factor receptor (EGFR) inhibitor compound 19 (CHMFL-EGFR-202), which potently inhibited EGFR primary mutants (L858R, del19) and drug-resistant mutant L858R/T790M.	ibrutinib	16-25	epidermal growth factor receptor	Homo sapiens	152-156
28282122-1	2017	On the basis of Ibrutinib"s core pharmacophore, which was moderately active to EGFR T790M mutant, we discovered novel epidermal growth factor receptor (EGFR) inhibitor compound 19 (CHMFL-EGFR-202), which potently inhibited EGFR primary mutants (L858R, del19) and drug-resistant mutant L858R/T790M.	ibrutinib	16-25	epidermal growth factor receptor	Homo sapiens	152-156
28299881-2	2017	In this study, we performed miR expression analysis using NanoString nCounter to discover differentially regulated miRs after therapy with the Bruton tyrosine kinase inhibitor ibrutinib.	ibrutinib	176-185	membrane associated ring-CH-type finger 8	Homo sapiens	28-31
28299881-3	2017	Of the differentially regulated miRs in the discovery set, miR-29c and miR-126 were confirmed using real-time PCR to be upregulated in CLL patient cells with ibrutinib therapy.	ibrutinib	158-167	microRNA 29c	Homo sapiens	59-66
28299881-3	2017	Of the differentially regulated miRs in the discovery set, miR-29c and miR-126 were confirmed using real-time PCR to be upregulated in CLL patient cells with ibrutinib therapy.	ibrutinib	158-167	microRNA 126	Homo sapiens	71-78
28352655-0	2017	Panobinostat acts synergistically with ibrutinib in diffuse large B cell lymphoma cells with MyD88 L265P mutations.	ibrutinib	39-48	MYD88 innate immune signal transduction adaptor	Homo sapiens	93-98
28352655-2	2017	While selective inhibition of BTK with ibrutinib causes clinical responses in relapsed DLBCL patients, most responses are partial and of a short duration.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	30-33
28352655-3	2017	Here, we demonstrated that MyD88 silencing enhanced ibrutinib efficacy in DLBCL cells harboring MyD88 L265P mutations.	ibrutinib	52-61	MYD88 innate immune signal transduction adaptor	Homo sapiens	27-32
28352655-3	2017	Here, we demonstrated that MyD88 silencing enhanced ibrutinib efficacy in DLBCL cells harboring MyD88 L265P mutations.	ibrutinib	52-61	MYD88 innate immune signal transduction adaptor	Homo sapiens	96-101
28352655-4	2017	Chemical downregulation of MyD88 expression with HDAC inhibitors also synergized with ibrutinib.	ibrutinib	86-95	MYD88 innate immune signal transduction adaptor	Homo sapiens	27-32
28352655-4	2017	Chemical downregulation of MyD88 expression with HDAC inhibitors also synergized with ibrutinib.	ibrutinib	86-95	histone deacetylase 9	Homo sapiens	49-53
28352655-6	2017	In turn, STAT3 silencing caused a decrease in MyD88 mRNA and protein levels, and enhanced the ibrutinib antilymphoma effect in MyD88 mutant DLBCL cells.	ibrutinib	94-103	signal transducer and activator of transcription 3	Homo sapiens	9-14
28352655-6	2017	In turn, STAT3 silencing caused a decrease in MyD88 mRNA and protein levels, and enhanced the ibrutinib antilymphoma effect in MyD88 mutant DLBCL cells.	ibrutinib	94-103	MYD88 innate immune signal transduction adaptor	Homo sapiens	127-132
28294689-12	2017	Ibrutinib is active in patients with WM and is affected by MYD88 and CXCR4 mutation status.	ibrutinib	0-9	C-X-C motif chemokine receptor 4	Homo sapiens	69-74
28294689-13	2017	Patients with mutated MYD88 and wild-type CXCR4 mutation status exhibit best responses to ibrutinib.	ibrutinib	90-99	MYD88 innate immune signal transduction adaptor	Homo sapiens	22-27
28294689-13	2017	Patients with mutated MYD88 and wild-type CXCR4 mutation status exhibit best responses to ibrutinib.	ibrutinib	90-99	C-X-C motif chemokine receptor 4	Homo sapiens	42-47
28294689-14	2017	Lower response rates and delayed responses to ibrutinib are associated with mutated CXCR4 in patients with WM.	ibrutinib	46-55	C-X-C motif chemokine receptor 4	Homo sapiens	84-89
28049639-1	2017	Disease progression in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib has been attributed to histologic transformation or acquired mutations in BTK and PLCG2.	ibrutinib	85-94	Bruton tyrosine kinase	Homo sapiens	169-172
28049639-1	2017	Disease progression in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib has been attributed to histologic transformation or acquired mutations in BTK and PLCG2.	ibrutinib	85-94	phospholipase C gamma 2	Homo sapiens	177-182
28407693-2	2017	Starting from ibrutinib, a highly potent irreversible BTK kinase inhibitor, which was also found to be moderately active to EGFR T790M mutant, we discovered a highly potent irreversible EGFR inhibitor CHMFL-EGFR-26, which is selectively potent against EGFR mutants including L858R, del19, and L858R/T790M.	ibrutinib	14-23	epidermal growth factor receptor	Mus musculus	186-190
28212557-3	2017	We used this high sensitivity assay in combination with Sanger sequencing and next generation sequencing (NGS) and tested cellular DNA and cell-free DNA (cfDNA) from patients with CLL treated with the BTK inhibitor, ibrutinib.	ibrutinib	216-225	Bruton tyrosine kinase	Homo sapiens	201-204
28407693-2	2017	Starting from ibrutinib, a highly potent irreversible BTK kinase inhibitor, which was also found to be moderately active to EGFR T790M mutant, we discovered a highly potent irreversible EGFR inhibitor CHMFL-EGFR-26, which is selectively potent against EGFR mutants including L858R, del19, and L858R/T790M.	ibrutinib	14-23	epidermal growth factor receptor	Mus musculus	124-128
28096090-1	2017	The introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib has dramatically changed the management of chronic lymphocytic leukemia (CLL).	ibrutinib	63-72	Bruton tyrosine kinase	Homo sapiens	24-46
28407693-2	2017	Starting from ibrutinib, a highly potent irreversible BTK kinase inhibitor, which was also found to be moderately active to EGFR T790M mutant, we discovered a highly potent irreversible EGFR inhibitor CHMFL-EGFR-26, which is selectively potent against EGFR mutants including L858R, del19, and L858R/T790M.	ibrutinib	14-23	epidermal growth factor receptor	Mus musculus	186-190
28407693-2	2017	Starting from ibrutinib, a highly potent irreversible BTK kinase inhibitor, which was also found to be moderately active to EGFR T790M mutant, we discovered a highly potent irreversible EGFR inhibitor CHMFL-EGFR-26, which is selectively potent against EGFR mutants including L858R, del19, and L858R/T790M.	ibrutinib	14-23	epidermal growth factor receptor	Mus musculus	186-190
28096090-1	2017	The introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib has dramatically changed the management of chronic lymphocytic leukemia (CLL).	ibrutinib	63-72	Bruton tyrosine kinase	Homo sapiens	48-51
28031181-0	2017	Ibrutinib inhibits pre-BCR+ B-cell acute lymphoblastic leukemia progression by targeting BTK and BLK.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	89-92
28031181-0	2017	Ibrutinib inhibits pre-BCR+ B-cell acute lymphoblastic leukemia progression by targeting BTK and BLK.	ibrutinib	0-9	B lymphoid kinase	Mus musculus	97-100
28031181-3	2017	Here, we investigated the activity and mechanism of action of the BTK inhibitor ibrutinib in preclinical models of B-ALL.	ibrutinib	80-89	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	66-69
28031181-5	2017	In pre-BCR+ ALL, ibrutinib thwarted autonomous and induced pre-BCR signaling, resulting in deactivation of PI3K/Akt signaling.	ibrutinib	17-26	thymoma viral proto-oncogene 1	Mus musculus	112-115
28031181-6	2017	Ibrutinib modulated the expression of pre-BCR regulators (PTPN6, CD22, CD72, and PKCbeta) and substantially reduced BCL6 levels.	ibrutinib	0-9	protein tyrosine phosphatase, non-receptor type 6	Mus musculus	58-63
28031181-6	2017	Ibrutinib modulated the expression of pre-BCR regulators (PTPN6, CD22, CD72, and PKCbeta) and substantially reduced BCL6 levels.	ibrutinib	0-9	CD22 antigen	Mus musculus	65-69
28031181-6	2017	Ibrutinib modulated the expression of pre-BCR regulators (PTPN6, CD22, CD72, and PKCbeta) and substantially reduced BCL6 levels.	ibrutinib	0-9	CD72 antigen	Mus musculus	71-75
28031181-6	2017	Ibrutinib modulated the expression of pre-BCR regulators (PTPN6, CD22, CD72, and PKCbeta) and substantially reduced BCL6 levels.	ibrutinib	0-9	protein kinase C, beta	Mus musculus	81-88
28031181-6	2017	Ibrutinib modulated the expression of pre-BCR regulators (PTPN6, CD22, CD72, and PKCbeta) and substantially reduced BCL6 levels.	ibrutinib	0-9	B cell leukemia/lymphoma 6	Mus musculus	116-120
28031181-7	2017	Ibrutinib inhibited ALL cell migration toward CXCL12 and beneath marrow stromal cells and reduced CD44 expression.	ibrutinib	0-9	chemokine (C-X-C motif) ligand 12	Mus musculus	46-52
28031181-7	2017	Ibrutinib inhibited ALL cell migration toward CXCL12 and beneath marrow stromal cells and reduced CD44 expression.	ibrutinib	0-9	CD44 antigen	Mus musculus	98-102
28031181-8	2017	CRISPR-Cas9 gene editing revealed that both BTK and B lymphocyte kinase (BLK) are relevant targets of ibrutinib in pre-BCR+ ALL.	ibrutinib	102-111	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	44-47
28031181-8	2017	CRISPR-Cas9 gene editing revealed that both BTK and B lymphocyte kinase (BLK) are relevant targets of ibrutinib in pre-BCR+ ALL.	ibrutinib	102-111	B lymphoid kinase	Mus musculus	52-71
28031181-8	2017	CRISPR-Cas9 gene editing revealed that both BTK and B lymphocyte kinase (BLK) are relevant targets of ibrutinib in pre-BCR+ ALL.	ibrutinib	102-111	B lymphoid kinase	Mus musculus	73-76
28130034-0	2017	NICE guidance on ibrutinib for previously treated chronic lymphocytic leukaemia and untreated chronic lymphocytic leukaemia in the presence of 17p deletion or TP53 mutation.	ibrutinib	17-26	tumor protein p53	Homo sapiens	159-163
28073846-2	2017	Ibrutinib has demonstrated single-agent efficacy and acceptable tolerability at doses of 420 and 840 mg in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who were treatment-naive (TN) or had relapsed/refractory (R/R) CLL after &gt;=1 prior therapy in a phase Ib/II study (PCYC-1102).	ibrutinib	0-9	solute carrier family 35 member B2	Homo sapiens	182-185
28073846-9	2017	Ibrutinib was well tolerated with extended follow-up; rates of grade &gt;=3 cytopenias and fatigue, as well as discontinuations due to toxicities decreased over time.Conclusions: Single-agent ibrutinib at 420 mg once-daily resulted in durable responses and was well tolerated with up to 44 months follow-up in patients with TN and R/R CLL/SLL.	ibrutinib	192-201	solute carrier family 35 member B2	Homo sapiens	339-342
28061447-0	2017	The combination effect of homoharringtonine and ibrutinib on FLT3-ITD mutant acute myeloid leukemia.	ibrutinib	48-57	fms related receptor tyrosine kinase 3	Homo sapiens	61-65
28199309-5	2017	Drugs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kdelta activity directly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B cells.	ibrutinib	74-83	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta	Homo sapiens	90-99
28199309-5	2017	Drugs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kdelta activity directly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B cells.	ibrutinib	74-83	activation induced cytidine deaminase	Homo sapiens	155-158
28199309-6	2017	Here we show that treatment of primary mouse B cells with idelalisib or duvelisib, and to a lesser extent ibrutinib, enhanced the expression of AID and increased somatic hypermutation and chromosomal translocation frequency to the Igh locus and to several AID off-target sites.	ibrutinib	106-115	activation-induced cytidine deaminase	Mus musculus	144-147
28199309-9	2017	Consistently, PI3Kdelta inhibitors enhanced AID expression and translocation frequency to IGH and AID off-target sites in human chronic lymphocytic leukaemia and mantle cell lymphoma cell lines, and patients treated with idelalisib, but not ibrutinib, showed increased somatic hypermutation in AID off-targets.	ibrutinib	241-250	activation induced cytidine deaminase	Homo sapiens	44-47
28061447-3	2017	In this study, we explored the inhibitory effect and mechanism of homoharringtonine (HHT) in combination with ibrutinib on FLT3-ITD mutant AML cells.	ibrutinib	110-119	fms related receptor tyrosine kinase 3	Homo sapiens	123-127
28061447-6	2017	Interestingly, synergistic cytotoxicity of ibrutinib and HHT was dependent on both FLT3 and BTK.	ibrutinib	43-52	fms related receptor tyrosine kinase 3	Homo sapiens	83-87
28061447-6	2017	Interestingly, synergistic cytotoxicity of ibrutinib and HHT was dependent on both FLT3 and BTK.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	92-95
28105602-4	2017	Likewise, a combination of ibrutinib, bendamustine and rituximab was more effective in previously-treated adults than bendamustine plus rituximab in a phase III placebo-controlled study (HELIOS).	ibrutinib	27-36	IKAROS family zinc finger 2	Homo sapiens	187-193
28088788-1	2017	Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	11-14
27535981-1	2017	Purpose: Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, is approved for the treatment of relapsed chronic lymphocytic leukemia (CLL) and CLL with del17p.	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	22-44
27535981-1	2017	Purpose: Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, is approved for the treatment of relapsed chronic lymphocytic leukemia (CLL) and CLL with del17p.	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	46-49
27535981-6	2017	Unmutated IGVH status, elevated ZAP70 expression, and trisomy 12 were associated with heightened sensitivity to ibrutinib treatment.	ibrutinib	112-121	zeta chain of T cell receptor associated protein kinase 70	Homo sapiens	32-37
27535981-8	2017	A validation sample of 15 CLL carrying TP53 mutations, of which 13 carried both del17p and a TP53 mutation, confirmed substantially less sensitivity to ibrutinib-induced apoptosis.Conclusions: This study identifies that CLL harboring del17p/TP53-mutated cells are substantially less sensitive to ibrutinib-induced apoptosis than del17p/TP53 wild-type cells.	ibrutinib	152-161	tumor protein p53	Homo sapiens	39-43
27535981-8	2017	A validation sample of 15 CLL carrying TP53 mutations, of which 13 carried both del17p and a TP53 mutation, confirmed substantially less sensitivity to ibrutinib-induced apoptosis.Conclusions: This study identifies that CLL harboring del17p/TP53-mutated cells are substantially less sensitive to ibrutinib-induced apoptosis than del17p/TP53 wild-type cells.	ibrutinib	152-161	tumor protein p53	Homo sapiens	93-97
27535981-8	2017	A validation sample of 15 CLL carrying TP53 mutations, of which 13 carried both del17p and a TP53 mutation, confirmed substantially less sensitivity to ibrutinib-induced apoptosis.Conclusions: This study identifies that CLL harboring del17p/TP53-mutated cells are substantially less sensitive to ibrutinib-induced apoptosis than del17p/TP53 wild-type cells.	ibrutinib	152-161	tumor protein p53	Homo sapiens	93-97
27535981-8	2017	A validation sample of 15 CLL carrying TP53 mutations, of which 13 carried both del17p and a TP53 mutation, confirmed substantially less sensitivity to ibrutinib-induced apoptosis.Conclusions: This study identifies that CLL harboring del17p/TP53-mutated cells are substantially less sensitive to ibrutinib-induced apoptosis than del17p/TP53 wild-type cells.	ibrutinib	152-161	tumor protein p53	Homo sapiens	93-97
27431016-4	2017	When evaluated in CLL cells from 38 patients pre and post treatment with ibrutinib, a subset of these miRNAs (miR-22, miR-34a, miR-146b and miR-181b) was significantly decreased in response to ibrutinib.	ibrutinib	73-82	microRNA 22	Homo sapiens	110-116
27431016-4	2017	When evaluated in CLL cells from 38 patients pre and post treatment with ibrutinib, a subset of these miRNAs (miR-22, miR-34a, miR-146b and miR-181b) was significantly decreased in response to ibrutinib.	ibrutinib	73-82	microRNA 34a	Homo sapiens	118-125
27431016-4	2017	When evaluated in CLL cells from 38 patients pre and post treatment with ibrutinib, a subset of these miRNAs (miR-22, miR-34a, miR-146b and miR-181b) was significantly decreased in response to ibrutinib.	ibrutinib	73-82	microRNA 146b	Homo sapiens	127-135
27431016-4	2017	When evaluated in CLL cells from 38 patients pre and post treatment with ibrutinib, a subset of these miRNAs (miR-22, miR-34a, miR-146b and miR-181b) was significantly decreased in response to ibrutinib.	ibrutinib	193-202	microRNA 22	Homo sapiens	110-116
27431016-4	2017	When evaluated in CLL cells from 38 patients pre and post treatment with ibrutinib, a subset of these miRNAs (miR-22, miR-34a, miR-146b and miR-181b) was significantly decreased in response to ibrutinib.	ibrutinib	193-202	microRNA 34a	Homo sapiens	118-125
27431016-4	2017	When evaluated in CLL cells from 38 patients pre and post treatment with ibrutinib, a subset of these miRNAs (miR-22, miR-34a, miR-146b and miR-181b) was significantly decreased in response to ibrutinib.	ibrutinib	193-202	microRNA 146b	Homo sapiens	127-135
27776353-1	2017	The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom"s macroglobulinemia.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	4-26
28138560-0	2017	Leukemia cell proliferation and death in chronic lymphocytic leukemia patients on therapy with the BTK inhibitor ibrutinib.	ibrutinib	113-122	Bruton tyrosine kinase	Homo sapiens	99-102
28138560-2	2017	Ibrutinib is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL) that inhibits Bruton"s tyrosine kinase (BTK), a kinase involved in B cell receptor signaling.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	110-134
28138560-2	2017	Ibrutinib is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL) that inhibits Bruton"s tyrosine kinase (BTK), a kinase involved in B cell receptor signaling.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	136-139
27776353-1	2017	The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom"s macroglobulinemia.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	28-31
27776353-2	2017	Acquired resistance to ibrutinib due to BTK C481S mutation has been reported.	ibrutinib	23-32	Bruton tyrosine kinase	Homo sapiens	40-43
27776353-3	2017	Mutations in PLCgamma2 can also mediate resistance to ibrutinib.	ibrutinib	54-63	phospholipase C gamma 2	Homo sapiens	13-22
28036258-9	2017	Moreover, evaluation of the CCL3 and CCL4 levels may be helpful for selecting DLBCL patients likely to benefit from doxorubicin treatment in combination with the velcade or ibrutinib.	ibrutinib	173-182	C-C motif chemokine ligand 3	Homo sapiens	28-32
28073005-4	2017	Inhibition of PI3Kalpha/delta resulted in tumor regression in an ibrutinib-resistant CD79BWT/MYD88mut patient-derived ABC-DLBCL model.	ibrutinib	65-74	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha	Homo sapiens	14-23
28073005-4	2017	Inhibition of PI3Kalpha/delta resulted in tumor regression in an ibrutinib-resistant CD79BWT/MYD88mut patient-derived ABC-DLBCL model.	ibrutinib	65-74	MYD88 innate immune signal transduction adaptor	Homo sapiens	93-98
28073005-6	2017	A combination of ibrutinib with the PI3Kalpha/delta inhibitor copanlisib produced a sustained complete response in vivo in CD79Bmut/MYD88mut ABC-DLBCL models.	ibrutinib	17-26	MYD88 innate immune signal transduction adaptor	Homo sapiens	132-137
27697038-3	2017	Ibrutinib is the most used inhibitor of BTK and has great tolerability and efficacy in chronic lymphocytic leukemia.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	40-43
28791187-5	2017	Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL) and MCL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	32-54
28286680-3	2017	We present a case illustrating the utility of MYD88 status in distinguishing atypical forms of WM from marginal zone lymphoma (MZL) and in selecting second-line therapy with ibrutinib.	ibrutinib	174-183	MYD88 innate immune signal transduction adaptor	Homo sapiens	46-51
28791187-5	2017	Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL) and MCL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	56-59
28185174-3	2017	Ibrutinib was proven as a primary choice for patients with the TP53 gene deletion/mutation, who otherwise have no active treatment available.	ibrutinib	0-9	tumor protein p53	Homo sapiens	63-67
29375920-1	2017	Background: Ibrutinib is a Bruton"s tyrosine kinase (BTK) inhibitor approved for second-line treatment for mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and Waldenstrom macroglobulinemia.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	27-51
29375920-1	2017	Background: Ibrutinib is a Bruton"s tyrosine kinase (BTK) inhibitor approved for second-line treatment for mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and Waldenstrom macroglobulinemia.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	53-56
28185174-1	2017	OPINION STATEMENT: A number of new treatment options have recently emerged for chronic lymphocytic leukemia (CLL) patients, including the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3-kinase (PI3K) delta isoform inhibitor idelalisib combined with rituximab, the Bcl-2 antagonist venetoclax, and the new anti-CD20 antibodies obinutuzumab and ofatumumab.	ibrutinib	179-188	Bruton tyrosine kinase	Homo sapiens	164-167
27677739-0	2017	Kinase inhibitor ibrutinib to prevent cytokine-release syndrome after anti-CD19 chimeric antigen receptor T cells for B-cell neoplasms.	ibrutinib	17-26	CD19 molecule	Homo sapiens	75-79
27287071-6	2016	Loss of function studies suggested a potential oncogenic role of Nampt in Waldenstrom macroglobulinemia cells, and BTK-inhibitor ibrutinib and FK866 resulted in a significant and synergistic anti-Waldenstrom macroglobulinemia cell death, regardless of MYD88 and CXCR4 mutational status.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	115-118
27282255-0	2017	Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant.	ibrutinib	63-72	Bruton tyrosine kinase	Homo sapiens	83-86
28592763-4	2017	Ibrutinib or lenalidomide was shown to be more effective in activated B-cell (ABC) -type-DLBCL than in germinal center B-cell type-DLBCL.	ibrutinib	0-9	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	78-81
27756747-6	2016	We have also made the novel and clinically relevant discovery that inhibition of HDAC induces the BTK-targeting miRs in ibrutinib-sensitive and resistant CLL to effectively reduce both wild-type and C481S-mutant BTK.	ibrutinib	120-129	Bruton tyrosine kinase	Homo sapiens	98-101
27756747-6	2016	We have also made the novel and clinically relevant discovery that inhibition of HDAC induces the BTK-targeting miRs in ibrutinib-sensitive and resistant CLL to effectively reduce both wild-type and C481S-mutant BTK.	ibrutinib	120-129	Bruton tyrosine kinase	Homo sapiens	212-215
27756747-7	2016	This finding identifies a novel strategy that may be promising as a therapeutic modality to eliminate the C481S-mutant BTK clone that drives resistance to ibrutinib and provides the rationale for a combination strategy that includes ibrutinib to dually target BTK to suppress its prosurvival signaling.	ibrutinib	155-164	Bruton tyrosine kinase	Homo sapiens	119-122
27756747-7	2016	This finding identifies a novel strategy that may be promising as a therapeutic modality to eliminate the C481S-mutant BTK clone that drives resistance to ibrutinib and provides the rationale for a combination strategy that includes ibrutinib to dually target BTK to suppress its prosurvival signaling.	ibrutinib	233-242	Bruton tyrosine kinase	Homo sapiens	119-122
27802969-1	2016	Ibrutinib, a potent and irreversible small-molecule inhibitor of both Bruton"s tyrosine kinase and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	70-94
27802969-1	2016	Ibrutinib, a potent and irreversible small-molecule inhibitor of both Bruton"s tyrosine kinase and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	99-129
27802969-1	2016	Ibrutinib, a potent and irreversible small-molecule inhibitor of both Bruton"s tyrosine kinase and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	131-134
27802969-8	2016	We postulate that ibrutinib augments the graft-versus-leukemia (GVL) benefit through a T-cell-mediated effect, most likely due to ITK inhibition.	ibrutinib	18-27	IL2 inducible T cell kinase	Homo sapiens	130-133
27287071-6	2016	Loss of function studies suggested a potential oncogenic role of Nampt in Waldenstrom macroglobulinemia cells, and BTK-inhibitor ibrutinib and FK866 resulted in a significant and synergistic anti-Waldenstrom macroglobulinemia cell death, regardless of MYD88 and CXCR4 mutational status.	ibrutinib	129-138	MYD88 innate immune signal transduction adaptor	Homo sapiens	252-257
27287071-6	2016	Loss of function studies suggested a potential oncogenic role of Nampt in Waldenstrom macroglobulinemia cells, and BTK-inhibitor ibrutinib and FK866 resulted in a significant and synergistic anti-Waldenstrom macroglobulinemia cell death, regardless of MYD88 and CXCR4 mutational status.	ibrutinib	129-138	C-X-C motif chemokine receptor 4	Homo sapiens	262-267
27587489-11	2016	The BTK inhibitor ibrutinib clusters with EGFR inhibitors, because it cross-reacts with EGFR.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
27960302-5	2016	We show that an analogue of the covalent Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib bearing a fumarate ester electrophile is vulnerable to enzymatic metabolism on a time-scale that preserves rapid and sustained BTK inhibition, while thwarting more slowly accumulating off-target reactivity in cell and animal models.	ibrutinib	82-91	Bruton tyrosine kinase	Homo sapiens	41-65
27960302-5	2016	We show that an analogue of the covalent Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib bearing a fumarate ester electrophile is vulnerable to enzymatic metabolism on a time-scale that preserves rapid and sustained BTK inhibition, while thwarting more slowly accumulating off-target reactivity in cell and animal models.	ibrutinib	82-91	Bruton tyrosine kinase	Homo sapiens	67-70
27960302-5	2016	We show that an analogue of the covalent Bruton"s tyrosine kinase (BTK) inhibitor Ibrutinib bearing a fumarate ester electrophile is vulnerable to enzymatic metabolism on a time-scale that preserves rapid and sustained BTK inhibition, while thwarting more slowly accumulating off-target reactivity in cell and animal models.	ibrutinib	82-91	Bruton tyrosine kinase	Homo sapiens	219-222
27913471-7	2016	These recently approved drugs (ibrutinib, idelalisib, and venetoclax) are reporting excellent outcomes, including patients with high-risk disease such as 17p deletion (17p-) or TP53 mutations (TP53mut).	ibrutinib	31-40	tumor protein p53	Homo sapiens	177-181
27198718-2	2016	Ibrutinib, a Bruton"s tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia.	ibrutinib	0-9	tumor protein p53	Homo sapiens	97-101
27677742-7	2016	As an example, ibrutinib reduces CLL cell chemoattraction by inhibiting macrophage secretion of CXCL13.	ibrutinib	15-24	C-X-C motif chemokine ligand 13	Homo sapiens	96-102
27587489-11	2016	The BTK inhibitor ibrutinib clusters with EGFR inhibitors, because it cross-reacts with EGFR.	ibrutinib	18-27	epidermal growth factor receptor	Homo sapiens	42-46
27678331-0	2016	Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth.	ibrutinib	0-9	epidermal growth factor receptor	Homo sapiens	19-23
27678331-1	2016	Ibrutinib is a potent, small-molecule Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	38-60
27587489-11	2016	The BTK inhibitor ibrutinib clusters with EGFR inhibitors, because it cross-reacts with EGFR.	ibrutinib	18-27	epidermal growth factor receptor	Homo sapiens	88-92
27678331-1	2016	Ibrutinib is a potent, small-molecule Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	62-65
27678331-11	2016	Ibrutinib"s unique dual spectrum of activity against both TEC family and ERBB kinases suggests broader applications of ibrutinib in oncology.	ibrutinib	0-9	epidermal growth factor receptor	Homo sapiens	73-77
27678331-2	2016	Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	66-69
27678331-4	2016	Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors.	ibrutinib	55-64	erb-b2 receptor tyrosine kinase 2	Homo sapiens	154-158
27678331-4	2016	Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors.	ibrutinib	55-64	epidermal growth factor receptor	Homo sapiens	159-163
27157620-1	2016	Targeting Bruton tyrosine kinase (BTK) by ibrutinib is an effective treatment for patients with relapsed/refractory mantle cell lymphoma (MCL).	ibrutinib	42-51	Bruton tyrosine kinase	Homo sapiens	10-32
27678331-5	2016	Among sensitive cell lines, breast cancer lines with HER2 overexpression were most potently inhibited by ibrutinib (&lt;100 nmol/L); in addition, the IC50s were lower than that of lapatinib and dacomitinib.	ibrutinib	105-114	erb-b2 receptor tyrosine kinase 2	Homo sapiens	53-57
27678331-6	2016	Inhibition of cell growth by ibrutinib coincided with downregulation of phosphorylation on HER2 and EGFR and their downstream targets, AKT and ERK.	ibrutinib	29-38	erb-b2 receptor tyrosine kinase 2	Homo sapiens	91-95
27678331-6	2016	Inhibition of cell growth by ibrutinib coincided with downregulation of phosphorylation on HER2 and EGFR and their downstream targets, AKT and ERK.	ibrutinib	29-38	epidermal growth factor receptor	Homo sapiens	100-104
27678331-6	2016	Inhibition of cell growth by ibrutinib coincided with downregulation of phosphorylation on HER2 and EGFR and their downstream targets, AKT and ERK.	ibrutinib	29-38	AKT serine/threonine kinase 1	Homo sapiens	135-138
27678331-6	2016	Inhibition of cell growth by ibrutinib coincided with downregulation of phosphorylation on HER2 and EGFR and their downstream targets, AKT and ERK.	ibrutinib	29-38	EPH receptor B2	Homo sapiens	143-146
27678331-8	2016	Furthermore, ibrutinib inhibited recombinant HER2 and EGFR activity that was resistant to dialysis and rapid dilution, suggesting an irreversible interaction.	ibrutinib	13-22	erb-b2 receptor tyrosine kinase 2	Homo sapiens	45-49
27678331-8	2016	Furthermore, ibrutinib inhibited recombinant HER2 and EGFR activity that was resistant to dialysis and rapid dilution, suggesting an irreversible interaction.	ibrutinib	13-22	epidermal growth factor receptor	Homo sapiens	54-58
27678331-9	2016	The dual activity toward TEC family (BTK and ITK) and ERBB family kinases was unique to ibrutinib, as ERBB inhibitors do not inhibit or covalently bind BTK or ITK.	ibrutinib	88-97	Bruton tyrosine kinase	Homo sapiens	37-40
27678331-9	2016	The dual activity toward TEC family (BTK and ITK) and ERBB family kinases was unique to ibrutinib, as ERBB inhibitors do not inhibit or covalently bind BTK or ITK.	ibrutinib	88-97	IL2 inducible T cell kinase	Homo sapiens	45-48
27678331-9	2016	The dual activity toward TEC family (BTK and ITK) and ERBB family kinases was unique to ibrutinib, as ERBB inhibitors do not inhibit or covalently bind BTK or ITK.	ibrutinib	88-97	epidermal growth factor receptor	Homo sapiens	54-58
27678331-9	2016	The dual activity toward TEC family (BTK and ITK) and ERBB family kinases was unique to ibrutinib, as ERBB inhibitors do not inhibit or covalently bind BTK or ITK.	ibrutinib	88-97	epidermal growth factor receptor	Homo sapiens	102-106
27157620-1	2016	Targeting Bruton tyrosine kinase (BTK) by ibrutinib is an effective treatment for patients with relapsed/refractory mantle cell lymphoma (MCL).	ibrutinib	42-51	Bruton tyrosine kinase	Homo sapiens	34-37
27157620-9	2016	Targeting BCL2 by the specific inhibitor ABT-199 synergized with ibrutinib in inhibiting growth of both ibrutinib-sensitive and -resistant cancer cells in vitro and in vivo.	ibrutinib	65-74	BCL2 apoptosis regulator	Homo sapiens	10-14
27157620-9	2016	Targeting BCL2 by the specific inhibitor ABT-199 synergized with ibrutinib in inhibiting growth of both ibrutinib-sensitive and -resistant cancer cells in vitro and in vivo.	ibrutinib	104-113	BCL2 apoptosis regulator	Homo sapiens	10-14
27157620-10	2016	These results suggest co-targeting of BTK and BCL2 as a new therapeutic strategy in MCL, especially for patients with primary resistance to ibrutinib.	ibrutinib	140-149	Bruton tyrosine kinase	Homo sapiens	38-41
27157620-10	2016	These results suggest co-targeting of BTK and BCL2 as a new therapeutic strategy in MCL, especially for patients with primary resistance to ibrutinib.	ibrutinib	140-149	BCL2 apoptosis regulator	Homo sapiens	46-50
27793034-8	2016	Combination of OTX015 with the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib led to cell cycle arrest then cell death, and combination with suboptimal doses of the ALK inhibitor CEP28122 caused cell cycle arrest.	ibrutinib	72-81	Bruton tyrosine kinase	Homo sapiens	31-55
27793034-8	2016	Combination of OTX015 with the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib led to cell cycle arrest then cell death, and combination with suboptimal doses of the ALK inhibitor CEP28122 caused cell cycle arrest.	ibrutinib	72-81	Bruton tyrosine kinase	Homo sapiens	57-60
27742706-0	2016	HSP90 inhibition overcomes ibrutinib resistance in mantle cell lymphoma.	ibrutinib	27-36	heat shock protein 90 alpha family class A member 1	Homo sapiens	0-5
27742706-1	2016	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib induces responses in 70% of patients with relapsed and refractory mantle cell lymphoma (MCL).	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	4-26
27742706-1	2016	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib induces responses in 70% of patients with relapsed and refractory mantle cell lymphoma (MCL).	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	28-31
27742706-4	2016	We reasoned that newer heat shock protein 90 (HSP90) inhibitors could overcome ibrutinib resistance by targeting multiple oncogenic pathways in MCL.	ibrutinib	79-88	heat shock protein 90 alpha family class A member 1	Homo sapiens	23-44
27742706-4	2016	We reasoned that newer heat shock protein 90 (HSP90) inhibitors could overcome ibrutinib resistance by targeting multiple oncogenic pathways in MCL.	ibrutinib	79-88	heat shock protein 90 alpha family class A member 1	Homo sapiens	46-51
27799566-8	2016	A small molecule JAK1 inhibitor cooperated with the BTK inhibitor ibrutinib in reducing IRF4 levels and acted synergistically to kill ABC DLBCL cells, suggesting that this combination should be evaluated in clinical trials.	ibrutinib	66-75	Bruton tyrosine kinase	Homo sapiens	52-55
27799566-8	2016	A small molecule JAK1 inhibitor cooperated with the BTK inhibitor ibrutinib in reducing IRF4 levels and acted synergistically to kill ABC DLBCL cells, suggesting that this combination should be evaluated in clinical trials.	ibrutinib	66-75	interferon regulatory factor 4	Homo sapiens	88-92
27713153-7	2016	Interestingly, forced expression of WT or mutant CCND1 increased resistance of MCL cell lines to ibrutinib, an FDA-approved Bruton tyrosine kinase inhibitor for MCL treatment.	ibrutinib	97-106	cyclin D1	Homo sapiens	49-54
27579538-11	2016	Moreover, treatment of CLL cells with PEITC and the BTK kinase inhibitor ibrutinib decreased anti-IgM-induced translation and induced cell death to a greater extent than either agent alone.	ibrutinib	73-82	Bruton tyrosine kinase	Homo sapiens	52-55
27713153-0	2016	CCND1 mutations increase protein stability and promote ibrutinib resistance in mantle cell lymphoma.	ibrutinib	55-64	cyclin D1	Homo sapiens	0-5
27713153-8	2016	The Y44D mutant sustained the resistance to ibrutinib even at supraphysiologic concentrations (5-10 muM).	ibrutinib	44-53	latexin	Homo sapiens	100-103
27713153-9	2016	Furthermore, primary MCL tumors with CCND1 mutations also expressed stable CCND1 protein and were resistant to ibrutinib.	ibrutinib	111-120	cyclin D1	Homo sapiens	37-42
27713153-10	2016	These findings uncover a new mechanism that is critical for the regulation of CCND1 protein levels, and is directly relevant to primary ibrutinib resistance in MCL.	ibrutinib	136-145	cyclin D1	Homo sapiens	78-83
27904766-0	2016	The role of PIM1 in the ibrutinib-resistant ABC subtype of diffuse large B-cell lymphoma.	ibrutinib	24-33	Pim-1 proto-oncogene, serine/threonine kinase	Homo sapiens	12-16
27813535-0	2016	Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells.	ibrutinib	89-98	ubiquitin specific peptidase 14	Mus musculus	46-51
27813535-0	2016	Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells.	ibrutinib	89-98	ubiquitin carboxyl-terminal esterase L5	Mus musculus	56-61
27813535-3	2016	Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome).	ibrutinib	125-134	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	144-147
27813535-3	2016	Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome).	ibrutinib	125-134	myeloid differentiation primary response gene 88	Mus musculus	148-153
27904766-0	2016	The role of PIM1 in the ibrutinib-resistant ABC subtype of diffuse large B-cell lymphoma.	ibrutinib	24-33	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	44-47
27904766-5	2016	Ibrutinib, a first-in-class, orally available covalent BTK inhibitor, has demonstrated clinical activity in several B-cell leukemias and lymphomas.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	55-58
27904766-6	2016	A phase 1/2 clinical trial of single-agent ibrutinib in relapsed and refractory DLBCL patients revealed an overall response rate of 37% in ABC-DLBCL patients.	ibrutinib	43-52	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	139-142
27904766-8	2016	Here we report the discovery of point mutations within the kinase PIM1 that reduce sensitivity to ibrutinib in ABC-DLBCL.	ibrutinib	98-107	Pim-1 proto-oncogene, serine/threonine kinase	Homo sapiens	66-70
27904766-8	2016	Here we report the discovery of point mutations within the kinase PIM1 that reduce sensitivity to ibrutinib in ABC-DLBCL.	ibrutinib	98-107	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	111-114
27904766-10	2016	The introduction of mutant PIM1 into an ABC-DLBCL cell line, TMD8, increased colony formation and decreased sensitivity to ibrutinib.	ibrutinib	123-132	Pim-1 proto-oncogene, serine/threonine kinase	Homo sapiens	27-31
27904766-10	2016	The introduction of mutant PIM1 into an ABC-DLBCL cell line, TMD8, increased colony formation and decreased sensitivity to ibrutinib.	ibrutinib	123-132	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	40-43
27904766-11	2016	In addition, ibrutinib-resistant cell lines generated by prolonged ibrutinib exposure in vitro upregulated PIM1 expression, consistent with a role for PIM1 in antagonizing ibrutinib activity.	ibrutinib	13-22	Pim-1 proto-oncogene, serine/threonine kinase	Homo sapiens	107-111
27904766-11	2016	In addition, ibrutinib-resistant cell lines generated by prolonged ibrutinib exposure in vitro upregulated PIM1 expression, consistent with a role for PIM1 in antagonizing ibrutinib activity.	ibrutinib	13-22	Pim-1 proto-oncogene, serine/threonine kinase	Homo sapiens	151-155
27904766-11	2016	In addition, ibrutinib-resistant cell lines generated by prolonged ibrutinib exposure in vitro upregulated PIM1 expression, consistent with a role for PIM1 in antagonizing ibrutinib activity.	ibrutinib	67-76	Pim-1 proto-oncogene, serine/threonine kinase	Homo sapiens	107-111
27904766-11	2016	In addition, ibrutinib-resistant cell lines generated by prolonged ibrutinib exposure in vitro upregulated PIM1 expression, consistent with a role for PIM1 in antagonizing ibrutinib activity.	ibrutinib	67-76	Pim-1 proto-oncogene, serine/threonine kinase	Homo sapiens	107-111
27367453-0	2016	Ibrutinib Dosing Strategies Based on Interaction Potential of CYP3A4 Perpetrators Using Physiologically Based Pharmacokinetic Modeling.	ibrutinib	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	62-68
27367453-1	2016	Based on ibrutinib pharmacokinetics and potential sensitivity towards CYP3A4-mediated drug-drug interactions (DDIs), a physiologically based pharmacokinetic approach was developed to mechanistically describe DDI with various CYP3A4 perpetrators in healthy men under fasting conditions.	ibrutinib	9-18	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	70-76
27367453-1	2016	Based on ibrutinib pharmacokinetics and potential sensitivity towards CYP3A4-mediated drug-drug interactions (DDIs), a physiologically based pharmacokinetic approach was developed to mechanistically describe DDI with various CYP3A4 perpetrators in healthy men under fasting conditions.	ibrutinib	9-18	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	225-231
27367453-4	2016	The ibrutinib dose should be reduced to 140 mg (quarter of maximal prescribed dose) when coadministered with moderate CYP3A4 inhibitors so that exposures remain within observed ranges at therapeutic doses.	ibrutinib	4-13	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	118-124
27367453-5	2016	Thus, dose recommendations for CYP3A4 perpetrator use during ibrutinib treatment were developed and approved for labeling.	ibrutinib	61-70	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	31-37
26980069-0	2016	Response to ibrutinib in a patient with IgG lymphoplasmacytic lymphoma carrying the MYD88 L265P gene mutation.	ibrutinib	12-21	MYD88 innate immune signal transduction adaptor	Homo sapiens	84-89
27686109-1	2016	INTRODUCTION: Ibrutinib, a first-in-class covalent inhibitor of Bruton"s tyrosine kinase (BTK), is approved in many countries for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) and for previously untreated disease with a 17p deletion and, most recently, as a frontline therapy for CLL.	ibrutinib	14-23	Bruton tyrosine kinase	Homo sapiens	64-88
27686109-1	2016	INTRODUCTION: Ibrutinib, a first-in-class covalent inhibitor of Bruton"s tyrosine kinase (BTK), is approved in many countries for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) and for previously untreated disease with a 17p deletion and, most recently, as a frontline therapy for CLL.	ibrutinib	14-23	Bruton tyrosine kinase	Homo sapiens	90-93
27686109-7	2016	Expert opinion: Ibrutinib represents a transformative advance in CLL management and has validated BTK as a therapeutic target in this disease, but has some limitations, leading to the emergence of other BTK inhibitors and mechanism-based combination strategies.	ibrutinib	16-25	Bruton tyrosine kinase	Homo sapiens	98-101
27686109-7	2016	Expert opinion: Ibrutinib represents a transformative advance in CLL management and has validated BTK as a therapeutic target in this disease, but has some limitations, leading to the emergence of other BTK inhibitors and mechanism-based combination strategies.	ibrutinib	16-25	Bruton tyrosine kinase	Homo sapiens	203-206
30512375-6	2016	For BCR inhibitors, we will limit to the most mature drugs that have obtained marketing authorization: inhibitors of Bruton tyrosine kinase (BTK) ibrutinib and phosphatidyinositol 3-kinase (PI3K) delta, idelalisib.	ibrutinib	146-155	Bruton tyrosine kinase	Homo sapiens	141-144
27657651-4	2016	The potential to induce autoimmune cytopenia has been studied mostly with ibrutinib, a first- in-class bruton kinase (BTK) inhibitor, licensed for the treatment of relapsed/refractory high-risk CLL.	ibrutinib	74-83	Bruton tyrosine kinase	Homo sapiens	103-116
27657651-4	2016	The potential to induce autoimmune cytopenia has been studied mostly with ibrutinib, a first- in-class bruton kinase (BTK) inhibitor, licensed for the treatment of relapsed/refractory high-risk CLL.	ibrutinib	74-83	Bruton tyrosine kinase	Homo sapiens	118-121
27626175-0	2016	Ibrutinib targets mutant-EGFR kinase with a distinct binding conformation.	ibrutinib	0-9	epidermal growth factor receptor	Mus musculus	25-29
27641927-0	2016	Ibrutinib inhibition of Bruton protein-tyrosine kinase (BTK) in the treatment of B cell neoplasms.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	56-59
27564106-0	2016	Preclinical investigation of ibrutinib, a Bruton"s kinase tyrosine (Btk) inhibitor, in suppressing glioma tumorigenesis and stem cell phenotypes.	ibrutinib	29-38	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	68-71
27564106-10	2016	In parallel, Ibrutinib (a Btk inhibitor) treatment led to a similar anti-tumorigenic response.	ibrutinib	13-22	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	26-29
27626175-4	2016	The biochemical binding affinity examination in the EGFR L858R/T790M kinase revealed that, comparing to more efficient irreversible inhibitor WZ4002 (Kd: 0.074 muM), Ibrutinib exhibited less efficient binding (Kd: 0.18 muM).	ibrutinib	166-175	epidermal growth factor receptor	Mus musculus	52-56
27626175-1	2016	Ibrutinib, a clinically approved irreversible BTK kinase inhibitor for Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL) etc, has been reported to be potent against EGFR mutant kinase and currently being evaluated in clinic for Non Small Cell Lung Cancer (NSCLC).	ibrutinib	0-9	epidermal growth factor receptor	Mus musculus	181-185
27626175-5	2016	An X-ray crystal structure of EGFR (T790M) in complex with Ibrutinib exhibited a unique DFG-in/c-Helix-out inactive binding conformation, which partially explained the less efficiency of covalent binding and provided insight for further development of highly efficient irreversible binding inhibitor for the EGFR mutant kinase.	ibrutinib	59-68	epidermal growth factor receptor	Mus musculus	30-34
27626175-2	2016	Through EGFR wt/mutant engineered isogenic BaF3 cell lines we confirmed the irreversible binding mode of Ibrutinib with EGFR wt/mutant kinase via Cys797.	ibrutinib	105-114	epidermal growth factor receptor	Mus musculus	8-12
27626175-5	2016	An X-ray crystal structure of EGFR (T790M) in complex with Ibrutinib exhibited a unique DFG-in/c-Helix-out inactive binding conformation, which partially explained the less efficiency of covalent binding and provided insight for further development of highly efficient irreversible binding inhibitor for the EGFR mutant kinase.	ibrutinib	59-68	epidermal growth factor receptor	Mus musculus	308-312
27626175-6	2016	These results also imply that, unlike the canonical irreversible inhibitor, sustained effective concentration might be required for Ibrutinib in order to achieve the maximal efficacy in the clinic application against EGFR driven NSCLC.	ibrutinib	132-141	epidermal growth factor receptor	Mus musculus	217-221
27626175-2	2016	Through EGFR wt/mutant engineered isogenic BaF3 cell lines we confirmed the irreversible binding mode of Ibrutinib with EGFR wt/mutant kinase via Cys797.	ibrutinib	105-114	epidermal growth factor receptor	Mus musculus	120-124
27626175-3	2016	However, comparing to typical irreversible EGFR inhibitor, such as WZ4002, the washing-out experiments revealed a much less efficient covalent binding for Ibrutinib.	ibrutinib	155-164	epidermal growth factor receptor	Mus musculus	43-47
28123879-5	2016	Meanwhile, ibrutinib drove Th1-selective pressure in T lymphocytes, thus, reducing the PD-1 and PDL-1 expression.	ibrutinib	11-20	negative elongation factor complex member C/D	Homo sapiens	27-30
27661115-5	2016	Indeed, the Ibrutinib/Nutlin-3 combination was effective in promoting cytotoxicity also in primary B-CLL samples carrying 17p13 deletion and/or TP53 mutations, already in therapy with Ibrutinib.	ibrutinib	12-21	transformation related protein 53	Mus musculus	144-148
27571029-1	2016	The Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib has shown impressive clinical efficacy in a range of B-cell malignancies.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
27571029-1	2016	The Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib has shown impressive clinical efficacy in a range of B-cell malignancies.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
27571029-3	2016	Ibrutinib is a covalent, irreversible inhibitor that modifies Cys481 in the ATP binding site of Btk and renders the enzyme inactive, thereby blocking B-cell receptor signal transduction.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	96-99
27571029-4	2016	Not surprisingly, Cys481 is the most commonly mutated Btk residue in cases of acquired resistance to ibrutinib.	ibrutinib	101-110	Bruton tyrosine kinase	Homo sapiens	54-57
27571029-6	2016	Herein, we describe noncovalent Btk inhibitors that differ from covalent inhibitors like ibrutinib in that they do not interact with Cys481, they potently inhibit the ibrutinib-resistant Btk C481S mutant in vitro and in cells, and they are exquisitely selective for Btk.	ibrutinib	167-176	Bruton tyrosine kinase	Homo sapiens	32-35
27571029-6	2016	Herein, we describe noncovalent Btk inhibitors that differ from covalent inhibitors like ibrutinib in that they do not interact with Cys481, they potently inhibit the ibrutinib-resistant Btk C481S mutant in vitro and in cells, and they are exquisitely selective for Btk.	ibrutinib	167-176	Bruton tyrosine kinase	Homo sapiens	187-190
27571029-6	2016	Herein, we describe noncovalent Btk inhibitors that differ from covalent inhibitors like ibrutinib in that they do not interact with Cys481, they potently inhibit the ibrutinib-resistant Btk C481S mutant in vitro and in cells, and they are exquisitely selective for Btk.	ibrutinib	167-176	Bruton tyrosine kinase	Homo sapiens	187-190
27571029-9	2016	This class of noncovalent Btk inhibitors may provide a treatment option to patients, especially those who have acquired resistance to ibrutinib by mutation of Cys481 or Thr474.	ibrutinib	134-143	Bruton tyrosine kinase	Homo sapiens	26-29
28123879-5	2016	Meanwhile, ibrutinib drove Th1-selective pressure in T lymphocytes, thus, reducing the PD-1 and PDL-1 expression.	ibrutinib	11-20	programmed cell death 1	Homo sapiens	87-91
28123879-5	2016	Meanwhile, ibrutinib drove Th1-selective pressure in T lymphocytes, thus, reducing the PD-1 and PDL-1 expression.	ibrutinib	11-20	CD274 molecule	Homo sapiens	96-101
27542411-0	2016	The Phospholipase Cgamma2 Mutants R665W and L845F Identified in Ibrutinib-resistant Chronic Lymphocytic Leukemia Patients Are Hypersensitive to the Rho GTPase Rac2 Protein.	ibrutinib	64-73	phospholipase C gamma 2	Homo sapiens	4-25
27626698-0	2016	Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	39-42
27626698-1	2016	Ibrutinib (ibr), a first-in-class Bruton tyrosine kinase (BTK) inhibitor, has demonstrated high response rates in both relapsed/refractory and treatment naive chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	34-56
27626698-1	2016	Ibrutinib (ibr), a first-in-class Bruton tyrosine kinase (BTK) inhibitor, has demonstrated high response rates in both relapsed/refractory and treatment naive chronic lymphocytic leukemia (CLL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	58-61
27626698-3	2016	Mutations affecting the C481 residue of BTK disrupt ibrutinib binding and have been characterized by us and others as the most common mechanism of ibrutinib resistance.	ibrutinib	52-61	Bruton tyrosine kinase	Homo sapiens	40-43
27626698-3	2016	Mutations affecting the C481 residue of BTK disrupt ibrutinib binding and have been characterized by us and others as the most common mechanism of ibrutinib resistance.	ibrutinib	147-156	Bruton tyrosine kinase	Homo sapiens	40-43
27626698-8	2016	Our study lends further insight into the diverse mechanisms of ibrutinib resistance that has important implications for the development of next-generation BTK inhibitors as well as mutation detection in relapsed patients.	ibrutinib	63-72	Bruton tyrosine kinase	Homo sapiens	155-158
27542411-5	2016	We suggest that R665W and L845F be referred to as allomorphic rather than hypermorphic mutations of PLCG2 Rerouting of the transmembrane signals emanating from BCR and converging on PLCgamma2 through Rac in ibrutinib-resistant CLL cells may provide novel drug treatment strategies to overcome ibrutinib resistance mediated by PLCG2 mutations or to prevent its development in ibrutinib-treated CLL patients.	ibrutinib	293-302	phospholipase C gamma 2	Homo sapiens	100-105
27542411-5	2016	We suggest that R665W and L845F be referred to as allomorphic rather than hypermorphic mutations of PLCG2 Rerouting of the transmembrane signals emanating from BCR and converging on PLCgamma2 through Rac in ibrutinib-resistant CLL cells may provide novel drug treatment strategies to overcome ibrutinib resistance mediated by PLCG2 mutations or to prevent its development in ibrutinib-treated CLL patients.	ibrutinib	293-302	BCR activator of RhoGEF and GTPase	Homo sapiens	160-163
27542411-5	2016	We suggest that R665W and L845F be referred to as allomorphic rather than hypermorphic mutations of PLCG2 Rerouting of the transmembrane signals emanating from BCR and converging on PLCgamma2 through Rac in ibrutinib-resistant CLL cells may provide novel drug treatment strategies to overcome ibrutinib resistance mediated by PLCG2 mutations or to prevent its development in ibrutinib-treated CLL patients.	ibrutinib	293-302	AKT serine/threonine kinase 1	Homo sapiens	200-203
27542411-0	2016	The Phospholipase Cgamma2 Mutants R665W and L845F Identified in Ibrutinib-resistant Chronic Lymphocytic Leukemia Patients Are Hypersensitive to the Rho GTPase Rac2 Protein.	ibrutinib	64-73	Rac family small GTPase 2	Homo sapiens	159-163
27542411-1	2016	Mutations in the gene encoding phospholipase C-gamma2 (PLCgamma2) have been shown to be associated with resistance to targeted therapy of chronic lymphocytic leukemia (CLL) with the Bruton"s tyrosine kinase inhibitor ibrutinib.	ibrutinib	217-226	phospholipase C gamma 2	Homo sapiens	31-53
27542411-1	2016	Mutations in the gene encoding phospholipase C-gamma2 (PLCgamma2) have been shown to be associated with resistance to targeted therapy of chronic lymphocytic leukemia (CLL) with the Bruton"s tyrosine kinase inhibitor ibrutinib.	ibrutinib	217-226	phospholipase C gamma 2	Homo sapiens	55-64
27542411-1	2016	Mutations in the gene encoding phospholipase C-gamma2 (PLCgamma2) have been shown to be associated with resistance to targeted therapy of chronic lymphocytic leukemia (CLL) with the Bruton"s tyrosine kinase inhibitor ibrutinib.	ibrutinib	217-226	Bruton tyrosine kinase	Homo sapiens	182-206
27542411-2	2016	The fact that two of these mutations, R665W and L845F, imparted upon PLCgamma2 an ~2-3-fold ibrutinib-insensitive increase in the concentration of cytosolic Ca2+ following ligation of the B cell antigen receptor (BCR) led to the assumption that the two mutants exhibit constitutively enhanced intrinsic activity.	ibrutinib	92-101	phospholipase C gamma 2	Homo sapiens	69-78
27542411-5	2016	We suggest that R665W and L845F be referred to as allomorphic rather than hypermorphic mutations of PLCG2 Rerouting of the transmembrane signals emanating from BCR and converging on PLCgamma2 through Rac in ibrutinib-resistant CLL cells may provide novel drug treatment strategies to overcome ibrutinib resistance mediated by PLCG2 mutations or to prevent its development in ibrutinib-treated CLL patients.	ibrutinib	207-216	phospholipase C gamma 2	Homo sapiens	100-105
27542411-5	2016	We suggest that R665W and L845F be referred to as allomorphic rather than hypermorphic mutations of PLCG2 Rerouting of the transmembrane signals emanating from BCR and converging on PLCgamma2 through Rac in ibrutinib-resistant CLL cells may provide novel drug treatment strategies to overcome ibrutinib resistance mediated by PLCG2 mutations or to prevent its development in ibrutinib-treated CLL patients.	ibrutinib	207-216	BCR activator of RhoGEF and GTPase	Homo sapiens	160-163
27542411-5	2016	We suggest that R665W and L845F be referred to as allomorphic rather than hypermorphic mutations of PLCG2 Rerouting of the transmembrane signals emanating from BCR and converging on PLCgamma2 through Rac in ibrutinib-resistant CLL cells may provide novel drug treatment strategies to overcome ibrutinib resistance mediated by PLCG2 mutations or to prevent its development in ibrutinib-treated CLL patients.	ibrutinib	207-216	phospholipase C gamma 2	Homo sapiens	182-191
27542411-5	2016	We suggest that R665W and L845F be referred to as allomorphic rather than hypermorphic mutations of PLCG2 Rerouting of the transmembrane signals emanating from BCR and converging on PLCgamma2 through Rac in ibrutinib-resistant CLL cells may provide novel drug treatment strategies to overcome ibrutinib resistance mediated by PLCG2 mutations or to prevent its development in ibrutinib-treated CLL patients.	ibrutinib	207-216	AKT serine/threonine kinase 1	Homo sapiens	200-203
27542411-5	2016	We suggest that R665W and L845F be referred to as allomorphic rather than hypermorphic mutations of PLCG2 Rerouting of the transmembrane signals emanating from BCR and converging on PLCgamma2 through Rac in ibrutinib-resistant CLL cells may provide novel drug treatment strategies to overcome ibrutinib resistance mediated by PLCG2 mutations or to prevent its development in ibrutinib-treated CLL patients.	ibrutinib	293-302	phospholipase C gamma 2	Homo sapiens	100-105
27542411-5	2016	We suggest that R665W and L845F be referred to as allomorphic rather than hypermorphic mutations of PLCG2 Rerouting of the transmembrane signals emanating from BCR and converging on PLCgamma2 through Rac in ibrutinib-resistant CLL cells may provide novel drug treatment strategies to overcome ibrutinib resistance mediated by PLCG2 mutations or to prevent its development in ibrutinib-treated CLL patients.	ibrutinib	293-302	BCR activator of RhoGEF and GTPase	Homo sapiens	160-163
27542411-5	2016	We suggest that R665W and L845F be referred to as allomorphic rather than hypermorphic mutations of PLCG2 Rerouting of the transmembrane signals emanating from BCR and converging on PLCgamma2 through Rac in ibrutinib-resistant CLL cells may provide novel drug treatment strategies to overcome ibrutinib resistance mediated by PLCG2 mutations or to prevent its development in ibrutinib-treated CLL patients.	ibrutinib	293-302	AKT serine/threonine kinase 1	Homo sapiens	200-203
27602755-2	2016	Ibrutinib, a potent inhibitor of Bruton"s tyrosine kinase (BTK), is able to counteract pro-survival signals in CLL cells.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	33-57
27602755-2	2016	Ibrutinib, a potent inhibitor of Bruton"s tyrosine kinase (BTK), is able to counteract pro-survival signals in CLL cells.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	59-62
27602755-5	2016	Our data show that ibrutinib targets BTK expressed by NLCs modifying their phenotype and function.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	37-40
27602755-7	2016	Accordingly, ibrutinib hampers LPS-mediated signaling, decreasing STAT1 phosphorylation, while allows IL-4-mediated STAT6 phosphorylation.	ibrutinib	13-22	signal transducer and activator of transcription 1	Homo sapiens	66-71
27602755-7	2016	Accordingly, ibrutinib hampers LPS-mediated signaling, decreasing STAT1 phosphorylation, while allows IL-4-mediated STAT6 phosphorylation.	ibrutinib	13-22	interleukin 4	Homo sapiens	102-106
27602755-7	2016	Accordingly, ibrutinib hampers LPS-mediated signaling, decreasing STAT1 phosphorylation, while allows IL-4-mediated STAT6 phosphorylation.	ibrutinib	13-22	signal transducer and activator of transcription 6	Homo sapiens	116-121
27602755-8	2016	In addition, NLCs treated with ibrutinib are able to protect CLL cells from drug-induced apoptosis partially through the secretion of IL-10.	ibrutinib	31-40	interleukin 10	Homo sapiens	134-139
27602755-9	2016	Results from patient samples obtained prior and after 1 month of treatment with ibrutinib show an accentuation of CD206, CD11b and Tie2 in the monocytic population in the peripheral blood.	ibrutinib	80-89	mannose receptor C-type 1	Homo sapiens	114-119
27602755-9	2016	Results from patient samples obtained prior and after 1 month of treatment with ibrutinib show an accentuation of CD206, CD11b and Tie2 in the monocytic population in the peripheral blood.	ibrutinib	80-89	integrin subunit alpha M	Homo sapiens	121-126
27602755-9	2016	Results from patient samples obtained prior and after 1 month of treatment with ibrutinib show an accentuation of CD206, CD11b and Tie2 in the monocytic population in the peripheral blood.	ibrutinib	80-89	TEK receptor tyrosine kinase	Homo sapiens	131-135
27480113-4	2016	We found that CD20 is directly upregulated by CXCR4 ligand stromal cell-derived factor 1 (SDF-1alpha, CXCL12) produced by stromal cells, and BTK-inhibitor ibrutinib and CXCR4-inhibitor plerixafor block SDF-1alpha-mediated CD20 upregulation.	ibrutinib	155-164	Bruton tyrosine kinase	Homo sapiens	141-144
27688783-1	2016	Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib.	ibrutinib	122-131	delta/notch like EGF repeat containing	Homo sapiens	24-27
27480113-0	2016	Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis.	ibrutinib	0-9	membrane spanning 4-domains A1	Homo sapiens	19-23
27480113-5	2016	Ibrutinib also downmodulated Mcl1 levels in CLL cells in vivo and in coculture with stromal cells.	ibrutinib	0-9	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	29-33
27480113-0	2016	Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis.	ibrutinib	0-9	C-X-C motif chemokine receptor 4	Homo sapiens	68-73
27480113-0	2016	Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis.	ibrutinib	0-9	C-X-C motif chemokine ligand 12	Homo sapiens	74-79
27590878-2	2016	Ibrutinib is the first-generation BTK inhibitor.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	34-37
27480113-2	2016	Here we show that interactions between leukemia cells and stromal cells (HS-5) upregulate CD20 on CLL cells and that administering ibrutinib downmodulates CD20 (MS4A1) expression in vivo.	ibrutinib	131-140	membrane spanning 4-domains A1	Homo sapiens	155-159
27480113-2	2016	Here we show that interactions between leukemia cells and stromal cells (HS-5) upregulate CD20 on CLL cells and that administering ibrutinib downmodulates CD20 (MS4A1) expression in vivo.	ibrutinib	131-140	membrane spanning 4-domains A1	Homo sapiens	161-166
27480113-4	2016	We found that CD20 is directly upregulated by CXCR4 ligand stromal cell-derived factor 1 (SDF-1alpha, CXCL12) produced by stromal cells, and BTK-inhibitor ibrutinib and CXCR4-inhibitor plerixafor block SDF-1alpha-mediated CD20 upregulation.	ibrutinib	155-164	membrane spanning 4-domains A1	Homo sapiens	14-18
27432877-5	2016	Approval of the BTK inhibitor ibrutinib in the United States and Europe represents a novel and effective treatment option for both treatment-naive and relapsing patients.	ibrutinib	30-39	Bruton tyrosine kinase	Homo sapiens	16-19
27590878-3	2016	Ibrutinib has off-target effects on EGFR, ITK, and Tec family kinases, which explains the untoward effects of ibrutinib.	ibrutinib	0-9	epidermal growth factor receptor	Homo sapiens	36-40
27590878-3	2016	Ibrutinib has off-target effects on EGFR, ITK, and Tec family kinases, which explains the untoward effects of ibrutinib.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	42-45
27590878-3	2016	Ibrutinib has off-target effects on EGFR, ITK, and Tec family kinases, which explains the untoward effects of ibrutinib.	ibrutinib	110-119	epidermal growth factor receptor	Homo sapiens	36-40
27590878-5	2016	The C481S mutation in the BTK kinase domain was reported to be a major mechanism of resistance to ibrutinib.	ibrutinib	98-107	Bruton tyrosine kinase	Homo sapiens	26-29
27256378-2	2016	In this study, we show that recently developed inhibitors of BTK, such as ibrutinib (PCI-32765), AVL-292, and CGI-1746, reduce breast cancer cell survival and prevent drug-resistant clones from arising.	ibrutinib	74-83	Bruton tyrosine kinase	Homo sapiens	61-64
27256378-3	2016	Ibrutinib treatment impacts HER2(+) breast cancer cell viability at lower concentrations than the established breast cancer therapeutic lapatinib.	ibrutinib	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	28-32
27256378-7	2016	HER2(+) breast cancer cell proliferation is blocked by ibrutinib even in the presence of these factors.	ibrutinib	55-64	erb-b2 receptor tyrosine kinase 2	Homo sapiens	0-4
27256378-9	2016	In vivo, ibrutinib inhibits HER2(+) xenograft tumor growth.	ibrutinib	9-18	erb-b2 receptor tyrosine kinase 2	Homo sapiens	28-32
27256378-4	2016	In addition to inhibiting BTK, ibrutinib, but not AVL-292 and CGI-1746, efficiently blocks the activation of EGFR, HER2, ErbB3, and ErbB4.	ibrutinib	31-40	Bruton tyrosine kinase	Homo sapiens	26-29
27256378-10	2016	Consistent with this, immunofluorescence analysis of xenograft tumors shows that ibrutinib reduces the phosphorylation of HER2, BTK, Akt, and Erk and histone H3 and increases cleaved caspase-3 signals.	ibrutinib	81-90	erb-b2 receptor tyrosine kinase 2	Homo sapiens	122-126
27256378-4	2016	In addition to inhibiting BTK, ibrutinib, but not AVL-292 and CGI-1746, efficiently blocks the activation of EGFR, HER2, ErbB3, and ErbB4.	ibrutinib	31-40	epidermal growth factor receptor	Homo sapiens	109-113
27256378-10	2016	Consistent with this, immunofluorescence analysis of xenograft tumors shows that ibrutinib reduces the phosphorylation of HER2, BTK, Akt, and Erk and histone H3 and increases cleaved caspase-3 signals.	ibrutinib	81-90	Bruton tyrosine kinase	Homo sapiens	128-131
27256378-4	2016	In addition to inhibiting BTK, ibrutinib, but not AVL-292 and CGI-1746, efficiently blocks the activation of EGFR, HER2, ErbB3, and ErbB4.	ibrutinib	31-40	erb-b2 receptor tyrosine kinase 2	Homo sapiens	115-119
27256378-10	2016	Consistent with this, immunofluorescence analysis of xenograft tumors shows that ibrutinib reduces the phosphorylation of HER2, BTK, Akt, and Erk and histone H3 and increases cleaved caspase-3 signals.	ibrutinib	81-90	AKT serine/threonine kinase 1	Homo sapiens	133-136
27256378-10	2016	Consistent with this, immunofluorescence analysis of xenograft tumors shows that ibrutinib reduces the phosphorylation of HER2, BTK, Akt, and Erk and histone H3 and increases cleaved caspase-3 signals.	ibrutinib	81-90	EPH receptor B2	Homo sapiens	142-145
27256378-4	2016	In addition to inhibiting BTK, ibrutinib, but not AVL-292 and CGI-1746, efficiently blocks the activation of EGFR, HER2, ErbB3, and ErbB4.	ibrutinib	31-40	erb-b2 receptor tyrosine kinase 3	Homo sapiens	121-126
27256378-10	2016	Consistent with this, immunofluorescence analysis of xenograft tumors shows that ibrutinib reduces the phosphorylation of HER2, BTK, Akt, and Erk and histone H3 and increases cleaved caspase-3 signals.	ibrutinib	81-90	caspase 3	Homo sapiens	183-192
27256378-4	2016	In addition to inhibiting BTK, ibrutinib, but not AVL-292 and CGI-1746, efficiently blocks the activation of EGFR, HER2, ErbB3, and ErbB4.	ibrutinib	31-40	erb-b2 receptor tyrosine kinase 4	Homo sapiens	132-137
27256378-11	2016	As BTK-C and HER2 are often coexpressed in human breast cancers, these observations indicate that BTK-C is a potential therapeutic target and that ibrutinib could be an effective drug especially for HER2(+) breast cancer.	ibrutinib	147-156	Bruton tyrosine kinase	Homo sapiens	3-8
27256378-11	2016	As BTK-C and HER2 are often coexpressed in human breast cancers, these observations indicate that BTK-C is a potential therapeutic target and that ibrutinib could be an effective drug especially for HER2(+) breast cancer.	ibrutinib	147-156	erb-b2 receptor tyrosine kinase 2	Homo sapiens	13-17
31360080-6	2016	Ibrutinib targets Bruton"s tyrosine kinase, a downstream protein in the B-cell receptor pathway that is overactivated by the MYD88 L265P mutation.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	18-42
27256378-11	2016	As BTK-C and HER2 are often coexpressed in human breast cancers, these observations indicate that BTK-C is a potential therapeutic target and that ibrutinib could be an effective drug especially for HER2(+) breast cancer.	ibrutinib	147-156	erb-b2 receptor tyrosine kinase 2	Homo sapiens	199-203
27493708-1	2016	Ibrutinib is an oral Bruton"s tyrosine kinase (BTK) inhibitor, which has recently gained approval by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with symptomatic Waldenstrom macroglobulinemia (WM).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	21-45
27493708-1	2016	Ibrutinib is an oral Bruton"s tyrosine kinase (BTK) inhibitor, which has recently gained approval by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with symptomatic Waldenstrom macroglobulinemia (WM).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	47-50
28573668-2	2017	BTK-C481S and -T474I, expressed in Ramos and NALM-6 cells, maintained BTK auto-phosphorylation under treatment with ibrutinib or dasatinib, respectively, which showed only modest cytotoxicity.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	0-3
27148767-3	2016	Most attention has focused on inhibitors of BTK kinase with ibrutinib already approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukaemia.	ibrutinib	60-69	Bruton tyrosine kinase	Homo sapiens	44-47
27235717-5	2016	This inhibition was significantly amplified by DXM addition to ibrutinib and was related to a significant decrease in the expression of the cell cycle regulatory proteins CDK4 and cyclin E. Apoptosis increased especially with DXM/ibrutinib combination and was associated with a significant decrease in Mcl-1 expression.	ibrutinib	230-239	cyclin dependent kinase 4	Homo sapiens	171-175
27235717-5	2016	This inhibition was significantly amplified by DXM addition to ibrutinib and was related to a significant decrease in the expression of the cell cycle regulatory proteins CDK4 and cyclin E. Apoptosis increased especially with DXM/ibrutinib combination and was associated with a significant decrease in Mcl-1 expression.	ibrutinib	230-239	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	302-307
31360080-6	2016	Ibrutinib targets Bruton"s tyrosine kinase, a downstream protein in the B-cell receptor pathway that is overactivated by the MYD88 L265P mutation.	ibrutinib	0-9	MYD88 innate immune signal transduction adaptor	Homo sapiens	125-130
31360080-7	2016	A seminal Phase II trial of ibrutinib in previously treated WM patients showed impressive response rates and confirmed the effects of MYD88 L265P and CXCR4 WHIM mutations in response to therapy.	ibrutinib	28-37	MYD88 innate immune signal transduction adaptor	Homo sapiens	134-139
31360080-7	2016	A seminal Phase II trial of ibrutinib in previously treated WM patients showed impressive response rates and confirmed the effects of MYD88 L265P and CXCR4 WHIM mutations in response to therapy.	ibrutinib	28-37	C-X-C motif chemokine receptor 4	Homo sapiens	150-155
27508020-0	2016	Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	10-13
27127301-3	2016	Recently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib demonstrated important clinical activity in MCL.	ibrutinib	53-62	Bruton tyrosine kinase	Homo sapiens	14-36
27127301-3	2016	Recently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib demonstrated important clinical activity in MCL.	ibrutinib	53-62	Bruton tyrosine kinase	Homo sapiens	38-41
27043332-0	2016	Cutaneous, Purpuric Painful Nodules Upon Addition of Ibrutinib to RCVP Therapy in a CLL Patient: A Distinctive Reaction Pattern Reflecting Iatrogenic Th2 to Th1 Milieu Reversal.	ibrutinib	53-62	negative elongation factor complex member C/D	Homo sapiens	157-160
27508020-6	2016	Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth.	ibrutinib	35-44	Bruton tyrosine kinase	Homo sapiens	14-17
27210433-1	2016	A series of novel 4,5,6-trisubstituted pyrimidines were designed as potent covalent Bruton"s tyrosine kinase (BTK) inhibitors based on the structure of ibrutinib by using a ring-opening strategy.	ibrutinib	152-161	Bruton tyrosine kinase	Homo sapiens	84-108
27508020-7	2016	Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals.	ibrutinib	85-94	Bruton tyrosine kinase	Homo sapiens	164-167
27210433-1	2016	A series of novel 4,5,6-trisubstituted pyrimidines were designed as potent covalent Bruton"s tyrosine kinase (BTK) inhibitors based on the structure of ibrutinib by using a ring-opening strategy.	ibrutinib	152-161	Bruton tyrosine kinase	Homo sapiens	110-113
27379948-2	2016	Although ibrutinib is the only BTK inhibitor that has been approved by the US Food and Drug Administration, several others are under investigation.	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	31-34
27143257-0	2016	HCK is a survival determinant transactivated by mutated MYD88, and a direct target of ibrutinib.	ibrutinib	86-95	HCK proto-oncogene, Src family tyrosine kinase	Homo sapiens	0-3
27268124-4	2016	CXCR4 mutations may interfere with treatment response to ibrutinib.	ibrutinib	57-66	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
27143257-3	2016	Ibrutinib, a pleiotropic kinase inhibitor that targets BTK, is highly active in patients with mutated MYD88.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	55-58
27143257-3	2016	Ibrutinib, a pleiotropic kinase inhibitor that targets BTK, is highly active in patients with mutated MYD88.	ibrutinib	0-9	MYD88 innate immune signal transduction adaptor	Homo sapiens	102-107
27143257-6	2016	Ibrutinib and the more potent HCK inhibitor A419259, blocked HCK activation and induced apoptosis in mutated MYD88 WM and ABC DLBCL cells.	ibrutinib	0-9	HCK proto-oncogene, Src family tyrosine kinase	Homo sapiens	61-64
27143257-6	2016	Ibrutinib and the more potent HCK inhibitor A419259, blocked HCK activation and induced apoptosis in mutated MYD88 WM and ABC DLBCL cells.	ibrutinib	0-9	MYD88 innate immune signal transduction adaptor	Homo sapiens	109-114
27143257-7	2016	Docking and pull-down studies confirmed that HCK was a target of ibrutinib.	ibrutinib	65-74	HCK proto-oncogene, Src family tyrosine kinase	Homo sapiens	45-48
27143257-8	2016	Ibrutinib and A419259 also blocked adenosine triphosphate binding to HCK, whereas transduction of mutated MYD88 expressing WM cells with a mutated HCK gatekeeper greatly increased the half maximal effective concentration for ibrutinib and A419259.	ibrutinib	0-9	HCK proto-oncogene, Src family tyrosine kinase	Homo sapiens	69-72
27143257-8	2016	Ibrutinib and A419259 also blocked adenosine triphosphate binding to HCK, whereas transduction of mutated MYD88 expressing WM cells with a mutated HCK gatekeeper greatly increased the half maximal effective concentration for ibrutinib and A419259.	ibrutinib	225-234	MYD88 innate immune signal transduction adaptor	Homo sapiens	106-111
27143257-8	2016	Ibrutinib and A419259 also blocked adenosine triphosphate binding to HCK, whereas transduction of mutated MYD88 expressing WM cells with a mutated HCK gatekeeper greatly increased the half maximal effective concentration for ibrutinib and A419259.	ibrutinib	225-234	HCK proto-oncogene, Src family tyrosine kinase	Homo sapiens	147-150
27143257-9	2016	The findings support that HCK expression and activation is triggered by mutated MYD88, supports the growth and survival of mutated MYD88 WM and ABC DLBCL cells, and is a direct target of ibrutinib.	ibrutinib	187-196	HCK proto-oncogene, Src family tyrosine kinase	Homo sapiens	26-29
27143257-9	2016	The findings support that HCK expression and activation is triggered by mutated MYD88, supports the growth and survival of mutated MYD88 WM and ABC DLBCL cells, and is a direct target of ibrutinib.	ibrutinib	187-196	MYD88 innate immune signal transduction adaptor	Homo sapiens	80-85
27143257-9	2016	The findings support that HCK expression and activation is triggered by mutated MYD88, supports the growth and survival of mutated MYD88 WM and ABC DLBCL cells, and is a direct target of ibrutinib.	ibrutinib	187-196	MYD88 innate immune signal transduction adaptor	Homo sapiens	131-136
27002119-7	2016	Importantly, the ability of the BCR-associated kinase inhibitors idelalisib and ibrutinib, approved for treatment of CLL and other B-cell malignancies, to inhibit anti-IgM-induced signalling was reduced following IL-4 pretreatment in samples from the majority of patients.	ibrutinib	80-89	interleukin 4	Homo sapiens	213-217
27095788-7	2016	Complete Mcl-1 downregulation was consistently achieved only with SYK inhibitors R406 and GS-9973 (entospletinib), whereas the BTK inhibitor ibrutinib and the PI3Kdelta inhibitor idelalisib in more than half of the cases had only a partial effect.	ibrutinib	141-150	Bruton tyrosine kinase	Homo sapiens	127-130
27284738-6	2016	We show that ibrutinib was effective in increasing survival, activating cellular programs outside the p53 pathway and did not place selective pressure on the remaining wild-type Trp53 allele.	ibrutinib	13-22	tumor protein p53	Homo sapiens	102-105
27224912-5	2016	Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR-inhibitor ibrutinib and NF-kappaB-inhibitor lenalidomide.	ibrutinib	140-149	caspase recruitment domain family member 11	Homo sapiens	65-71
27284738-0	2016	p53-independent ibrutinib responses in an Emu-TCL1 mouse model demonstrates efficacy in high-risk CLL.	ibrutinib	16-25	transformation related protein 53	Mus musculus	0-3
27284738-7	2016	These data provide evidence that ibrutinib acts as an effective treatment for aggressive forms of CLL with TP53 mutations.	ibrutinib	33-42	tumor protein p53	Homo sapiens	107-111
27284738-0	2016	p53-independent ibrutinib responses in an Emu-TCL1 mouse model demonstrates efficacy in high-risk CLL.	ibrutinib	16-25	T cell lymphoma breakpoint 1	Mus musculus	46-50
27284738-5	2016	Herein, we used a CLL mouse model (Emu-TCL1) harboring one of the most common TP53 hot-spot mutations observed in CLL (p53(R172H), corresponding to p53(R175H) in humans) to evaluate its impact on disease progression, survival, response to therapy and loss of the remaining wild-type Trp53 allele following ibrutinib treatment.	ibrutinib	306-315	transformation related protein 53	Mus musculus	78-82
27284738-5	2016	Herein, we used a CLL mouse model (Emu-TCL1) harboring one of the most common TP53 hot-spot mutations observed in CLL (p53(R172H), corresponding to p53(R175H) in humans) to evaluate its impact on disease progression, survival, response to therapy and loss of the remaining wild-type Trp53 allele following ibrutinib treatment.	ibrutinib	306-315	transformation related protein 53	Mus musculus	119-122
27825463-2	2016	Ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor was FDA-approved in 2015 as the first ever drug for the treatment of WM.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	13-37
26961147-8	2016	Strong synergism was observed with pimasertib combined with the PI3K inhibitor idelalisib and the BTK inhibitor ibrutinib in cell lines derived from diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma.	ibrutinib	112-121	Bruton tyrosine kinase	Homo sapiens	98-101
27825463-2	2016	Ibrutinib, a Bruton"s tyrosine kinase (BTK) inhibitor was FDA-approved in 2015 as the first ever drug for the treatment of WM.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	39-42
27825466-6	2016	The BTK inhibitor ibrutinib was recently approved for patients with WM, and is a new option for selected newly diagnosed or relapsing patients.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
27825467-5	2016	As a result of these findings and based on the design and execution of a prospective clinical trial, the FDA granted approval to ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, to treat patients with symptomatic WM.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	148-170
27825467-5	2016	As a result of these findings and based on the design and execution of a prospective clinical trial, the FDA granted approval to ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, to treat patients with symptomatic WM.	ibrutinib	129-138	Bruton tyrosine kinase	Homo sapiens	172-175
26752141-1	2016	Ibrutinib, a recently approved inhibitor of Bruton"s tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	44-68
26819453-0	2016	The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma.	ibrutinib	34-43	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	20-23
26752141-1	2016	Ibrutinib, a recently approved inhibitor of Bruton"s tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	70-73
26819453-0	2016	The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma.	ibrutinib	34-43	CD19 antigen	Mus musculus	52-56
27082823-6	2016	Results indicated that MTDH, beta-catenin and lymphoid-enhancing factor-1 were inhibited subsequent to ibrutinib treatment.	ibrutinib	103-112	metadherin	Homo sapiens	23-27
27231694-1	2016	Ibrutinib (Imbruvica; Pharmacyclics) is the first Food and Drug Administration-approved inhibitor of Burton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	127-130
27199251-1	2016	Resistance to the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	18-42
27199251-1	2016	Resistance to the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	44-47
27199251-1	2016	Resistance to the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules.	ibrutinib	59-68	Bruton tyrosine kinase	Homo sapiens	112-115
27199251-6	2016	Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance.	ibrutinib	113-122	TNF superfamily member 10	Homo sapiens	22-27
27231694-1	2016	Ibrutinib (Imbruvica; Pharmacyclics) is the first Food and Drug Administration-approved inhibitor of Burton"s tyrosine kinase (BTK).	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	127-130
26582643-2	2016	The importance of BTK in cell trafficking is emphasized by the clonal contraction proceeded by lymphocytosis typical for the enzyme inhibitor, ibrutinib, in B-cell malignancies, including chronic lymphocytic leukemia (CLL).	ibrutinib	143-152	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	18-21
26880800-3	2016	Ibrutinib, an irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and IL2-inducible T-cell kinase (ITK), is in clinical use for the treatment of B-cell malignancies.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	40-64
26880800-3	2016	Ibrutinib, an irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and IL2-inducible T-cell kinase (ITK), is in clinical use for the treatment of B-cell malignancies.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	66-69
26880800-3	2016	Ibrutinib, an irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and IL2-inducible T-cell kinase (ITK), is in clinical use for the treatment of B-cell malignancies.	ibrutinib	0-9	IL2 inducible T cell kinase	Mus musculus	75-102
26880800-3	2016	Ibrutinib, an irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and IL2-inducible T-cell kinase (ITK), is in clinical use for the treatment of B-cell malignancies.	ibrutinib	0-9	IL2 inducible T cell kinase	Mus musculus	104-107
26880800-4	2016	Here, we report that BTK is expressed by murine and human MDSCs, and that ibrutinib is able to inhibit BTK phosphorylation in these cells.	ibrutinib	74-83	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	21-24
26880800-4	2016	Here, we report that BTK is expressed by murine and human MDSCs, and that ibrutinib is able to inhibit BTK phosphorylation in these cells.	ibrutinib	74-83	Bruton tyrosine kinase	Homo sapiens	103-106
26880800-6	2016	In addition, ibrutinib inhibited in vitro generation of human MDSCs and reduced mRNA expression of indolamine 2,3-dioxygenase, an immunosuppressive factor.	ibrutinib	13-22	indoleamine 2,3-dioxygenase 1	Homo sapiens	99-125
27029059-7	2016	However, co-administering alphaSlamf6 with the Bruton tyrosine kinase (Btk) inhibitor, ibrutinib, synergized to efficiently eliminate the tumor cells in the spleen, bone marrow, liver and the peritoneal cavity.	ibrutinib	87-96	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	47-69
27029059-7	2016	However, co-administering alphaSlamf6 with the Bruton tyrosine kinase (Btk) inhibitor, ibrutinib, synergized to efficiently eliminate the tumor cells in the spleen, bone marrow, liver and the peritoneal cavity.	ibrutinib	87-96	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	71-74
27029059-8	2016	Because an anti-human SLAMF6 mAb efficiently killed human CLL cells in vitro and in vivo, we propose that a combination of alphaSlamf6 with ibrutinib should be considered as a novel therapeutic approach for CLL and other B cell tumors.	ibrutinib	140-149	SLAM family member 6	Homo sapiens	22-28
26914495-1	2016	Although targeting the Bruton tyrosine kinase (BTK) with ibrutinib has changed lymphoma treatment, patients with mantle cell lymphoma (MCL) remain incurable.	ibrutinib	57-66	Bruton tyrosine kinase	Homo sapiens	23-45
26914495-1	2016	Although targeting the Bruton tyrosine kinase (BTK) with ibrutinib has changed lymphoma treatment, patients with mantle cell lymphoma (MCL) remain incurable.	ibrutinib	57-66	Bruton tyrosine kinase	Homo sapiens	47-50
26914495-7	2016	Interestingly, targeting PKC and BTK at the same time led to ibrutinib-mediated rescue of a weak sotrastaurin-induced apoptosis in MINO cells.	ibrutinib	61-70	proline rich transmembrane protein 2	Homo sapiens	25-28
26914495-7	2016	Interestingly, targeting PKC and BTK at the same time led to ibrutinib-mediated rescue of a weak sotrastaurin-induced apoptosis in MINO cells.	ibrutinib	61-70	Bruton tyrosine kinase	Homo sapiens	33-36
26880800-8	2016	Ibrutinib treatment also resulted in a significant reduction of MDSCs in wild-type mice bearing B16F10 melanoma tumors, but not in X-linked immunodeficiency mice (XID) harboring a BTK mutation, suggesting that BTK inhibition plays an important role in the observed reduction of MDSCs in vivo Finally, ibrutinib significantly enhanced the efficacy of anti-PD-L1 (CD274) therapy in a murine breast cancer model.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	180-183
26880800-8	2016	Ibrutinib treatment also resulted in a significant reduction of MDSCs in wild-type mice bearing B16F10 melanoma tumors, but not in X-linked immunodeficiency mice (XID) harboring a BTK mutation, suggesting that BTK inhibition plays an important role in the observed reduction of MDSCs in vivo Finally, ibrutinib significantly enhanced the efficacy of anti-PD-L1 (CD274) therapy in a murine breast cancer model.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	210-213
26880800-8	2016	Ibrutinib treatment also resulted in a significant reduction of MDSCs in wild-type mice bearing B16F10 melanoma tumors, but not in X-linked immunodeficiency mice (XID) harboring a BTK mutation, suggesting that BTK inhibition plays an important role in the observed reduction of MDSCs in vivo Finally, ibrutinib significantly enhanced the efficacy of anti-PD-L1 (CD274) therapy in a murine breast cancer model.	ibrutinib	0-9	CD274 antigen	Mus musculus	355-360
26880800-8	2016	Ibrutinib treatment also resulted in a significant reduction of MDSCs in wild-type mice bearing B16F10 melanoma tumors, but not in X-linked immunodeficiency mice (XID) harboring a BTK mutation, suggesting that BTK inhibition plays an important role in the observed reduction of MDSCs in vivo Finally, ibrutinib significantly enhanced the efficacy of anti-PD-L1 (CD274) therapy in a murine breast cancer model.	ibrutinib	0-9	CD274 antigen	Mus musculus	362-367
26660519-11	2016	Consistent with direct inhibition of T cells, ibrutinib inhibited Th17 differentiation of murine CD4(+)T cells in vitro Finally, in the bone marrow microenvironment, we found that ibrutinib disaggregated the interactions of macrophages and CLL cells, inhibited secretion of CXCL13, and decreased the chemoattraction of CLL cells.	ibrutinib	46-55	CD4 antigen	Mus musculus	97-100
26660519-11	2016	Consistent with direct inhibition of T cells, ibrutinib inhibited Th17 differentiation of murine CD4(+)T cells in vitro Finally, in the bone marrow microenvironment, we found that ibrutinib disaggregated the interactions of macrophages and CLL cells, inhibited secretion of CXCL13, and decreased the chemoattraction of CLL cells.	ibrutinib	46-55	chemokine (C-X-C motif) ligand 13	Mus musculus	274-280
26660519-11	2016	Consistent with direct inhibition of T cells, ibrutinib inhibited Th17 differentiation of murine CD4(+)T cells in vitro Finally, in the bone marrow microenvironment, we found that ibrutinib disaggregated the interactions of macrophages and CLL cells, inhibited secretion of CXCL13, and decreased the chemoattraction of CLL cells.	ibrutinib	180-189	chemokine (C-X-C motif) ligand 13	Mus musculus	274-280
26582643-4	2016	Inhibiting BTK by ibrutinib reduced surface membrane (sm) levels of CXCR4 but not CXCR5, CD49d and other adhesion/homing receptors.	ibrutinib	18-27	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	11-14
26582643-4	2016	Inhibiting BTK by ibrutinib reduced surface membrane (sm) levels of CXCR4 but not CXCR5, CD49d and other adhesion/homing receptors.	ibrutinib	18-27	chemokine (C-X-C motif) receptor 4	Mus musculus	68-73
27161742-15	2016	In all patients vWF levels were higher at the onset of the disease (169+-38%) and reduced up to normal values under Ibrutinib treatment (111.4+-47%).	ibrutinib	116-125	von Willebrand factor	Homo sapiens	16-19
27040703-6	2016	Ibrutinib, a first in class oral inhibitor of Btk, has shown promise as a very effective agent in the treatment of CLL-in both relapsed and upfront therapy, alone and in combination with other therapies, and in patients of all-risk disease-which has led to its approval in relapsed CLL and as frontline therapy in patients with the high-risk del(17p13) disease.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	46-49
27040702-5	2016	Patients with a del(17p) or TP53 mutation should be treated with the kinase inhibitors ibrutinib or a combination of idelalisib and rituximab.	ibrutinib	87-96	tumor protein p53	Homo sapiens	28-32
26957112-2	2016	The first-in-class Bruton"s tyrosine kinase (BTK) inhibitor, ibrutinib, has been in clinical use for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom"s macroglobulinemia.	ibrutinib	61-70	Bruton tyrosine kinase	Homo sapiens	19-43
26953281-2	2016	SUMMARY: Ibrutinib is a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK) approved for treatment of relapsed chronic lymphocytic leukemia (CLL).	ibrutinib	9-18	inhibitor of Bruton tyrosine kinase	Homo sapiens	44-79
26953281-2	2016	SUMMARY: Ibrutinib is a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK) approved for treatment of relapsed chronic lymphocytic leukemia (CLL).	ibrutinib	9-18	Bruton tyrosine kinase	Homo sapiens	81-84
26953281-11	2016	CONCLUSION: Ibrutinib is a first-in-class, orally active, irreversible BTK inhibitor with a novel mechanism of action.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	71-74
27471620-0	2016	A Tec kinase BTK inhibitor ibrutinib promotes maturation and activation of dendritic cells.	ibrutinib	27-36	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	13-16
27471620-1	2016	Ibrutinib, a BTK inhibitor, is currently used to treat various hematological malignancies.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	13-16
26957112-2	2016	The first-in-class Bruton"s tyrosine kinase (BTK) inhibitor, ibrutinib, has been in clinical use for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom"s macroglobulinemia.	ibrutinib	61-70	Bruton tyrosine kinase	Homo sapiens	45-48
27471620-3	2016	Ibrutinib treatment increased the proportion of CD11c(+) DCs, upregulated the expression of MHC-II and CD80 and downregulated Ly6C expression by DCs.	ibrutinib	0-9	integrin alpha X	Mus musculus	48-53
26813675-4	2016	We found that &gt;=5 cycles of ibrutinib therapy improved the expansion of CD19-directed CAR T cells (CTL019), in association with decreased expression of the immunosuppressive molecule programmed cell death 1 on T cells and of CD200 on B-CLL cells.	ibrutinib	31-40	CD19 molecule	Homo sapiens	75-79
27471620-3	2016	Ibrutinib treatment increased the proportion of CD11c(+) DCs, upregulated the expression of MHC-II and CD80 and downregulated Ly6C expression by DCs.	ibrutinib	0-9	histocompatibility-2, MHC	Mus musculus	92-98
27471620-3	2016	Ibrutinib treatment increased the proportion of CD11c(+) DCs, upregulated the expression of MHC-II and CD80 and downregulated Ly6C expression by DCs.	ibrutinib	0-9	CD80 antigen	Mus musculus	103-107
27471620-3	2016	Ibrutinib treatment increased the proportion of CD11c(+) DCs, upregulated the expression of MHC-II and CD80 and downregulated Ly6C expression by DCs.	ibrutinib	0-9	lymphocyte antigen 6 complex, locus C1	Mus musculus	126-130
27471620-4	2016	Additionally, ibrutinib treatment led to an increase in MHC-II(+), CD80(+) and CCR7(+) DCs but a decrease in CD86(+) DCs upon LPS stimulation.	ibrutinib	14-23	histocompatibility-2, MHC	Mus musculus	56-62
27471620-4	2016	Additionally, ibrutinib treatment led to an increase in MHC-II(+), CD80(+) and CCR7(+) DCs but a decrease in CD86(+) DCs upon LPS stimulation.	ibrutinib	14-23	CD80 antigen	Mus musculus	67-71
27471620-4	2016	Additionally, ibrutinib treatment led to an increase in MHC-II(+), CD80(+) and CCR7(+) DCs but a decrease in CD86(+) DCs upon LPS stimulation.	ibrutinib	14-23	CD86 antigen	Mus musculus	109-113
27471620-4	2016	Additionally, ibrutinib treatment led to an increase in MHC-II(+), CD80(+) and CCR7(+) DCs but a decrease in CD86(+) DCs upon LPS stimulation.	ibrutinib	14-23	toll-like receptor 4	Mus musculus	126-129
27471620-5	2016	LPS/ibrutinib-treated DCs displayed increased IFNbeta and IL-10 synthesis and decreased IL-6, IL-12 and NO production compared to DCs stimulated with LPS alone.	ibrutinib	4-13	toll-like receptor 4	Mus musculus	0-3
27471620-5	2016	LPS/ibrutinib-treated DCs displayed increased IFNbeta and IL-10 synthesis and decreased IL-6, IL-12 and NO production compared to DCs stimulated with LPS alone.	ibrutinib	4-13	interleukin 10	Mus musculus	58-63
27471620-5	2016	LPS/ibrutinib-treated DCs displayed increased IFNbeta and IL-10 synthesis and decreased IL-6, IL-12 and NO production compared to DCs stimulated with LPS alone.	ibrutinib	4-13	interleukin 6	Mus musculus	88-92
27471620-5	2016	LPS/ibrutinib-treated DCs displayed increased IFNbeta and IL-10 synthesis and decreased IL-6, IL-12 and NO production compared to DCs stimulated with LPS alone.	ibrutinib	4-13	toll-like receptor 4	Mus musculus	150-153
27471620-6	2016	Finally, LPS/ibrutinib-treated DCs promoted higher rates of CD4(+) T cell proliferation and cytokine production compared to LPS only stimulated DCs.	ibrutinib	13-22	CD4 antigen	Mus musculus	60-63
27471620-7	2016	Taken together, our results indicate that ibrutinib enhances the maturation and activation of DCs to promote CD4(+) T cell activation which could be exploited for the development of DC-based cancer therapies.	ibrutinib	42-51	CD4 antigen	Mus musculus	109-112
26659727-3	2016	Because of its role in hematopoietic cell signaling, Btk has become a target in the treatment of chronic lymphocytic leukemia and mantle cell lymphoma; the covalent Btk inhibitor ibrutinib was recently approved by the US Food and Drug Administration for treatment of these conditions.	ibrutinib	179-188	Bruton tyrosine kinase	Homo sapiens	53-56
26659727-3	2016	Because of its role in hematopoietic cell signaling, Btk has become a target in the treatment of chronic lymphocytic leukemia and mantle cell lymphoma; the covalent Btk inhibitor ibrutinib was recently approved by the US Food and Drug Administration for treatment of these conditions.	ibrutinib	179-188	Bruton tyrosine kinase	Homo sapiens	165-168
26659727-6	2016	Our results show that irreversible inhibition of Btk with two ibrutinib analogs in vitro decreased human platelet activation, phosphorylation of Btk, P-selectin exposure, spreading on fibrinogen, and aggregation under shear flow conditions.	ibrutinib	62-71	Bruton tyrosine kinase	Homo sapiens	49-52
26659727-6	2016	Our results show that irreversible inhibition of Btk with two ibrutinib analogs in vitro decreased human platelet activation, phosphorylation of Btk, P-selectin exposure, spreading on fibrinogen, and aggregation under shear flow conditions.	ibrutinib	62-71	Bruton tyrosine kinase	Homo sapiens	145-148
26659727-6	2016	Our results show that irreversible inhibition of Btk with two ibrutinib analogs in vitro decreased human platelet activation, phosphorylation of Btk, P-selectin exposure, spreading on fibrinogen, and aggregation under shear flow conditions.	ibrutinib	62-71	selectin P	Homo sapiens	150-160
26193078-4	2016	Novel small molecule inhibitors, including the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib and the phosphoinositide-3-kinase delta (PI3Kdelta) inhibitor idelalisib, target BCR signaling and have become the most successful new therapeutics in this disease.	ibrutinib	88-97	Bruton tyrosine kinase	Homo sapiens	47-71
26813675-4	2016	We found that &gt;=5 cycles of ibrutinib therapy improved the expansion of CD19-directed CAR T cells (CTL019), in association with decreased expression of the immunosuppressive molecule programmed cell death 1 on T cells and of CD200 on B-CLL cells.	ibrutinib	31-40	CD200 molecule	Homo sapiens	228-233
26715645-4	2016	Treatment of PDAC-bearing mice with the BTK inhibitor PCI32765 (ibrutinib) or by PI3Kgamma inhibition reprogrammed macrophages toward a T(H)1 phenotype that fostered CD8(+) T-cell cytotoxicity, and suppressed PDAC growth, indicating that BTK signaling mediates PDAC immunosuppression.	ibrutinib	54-62	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	40-43
26715645-4	2016	Treatment of PDAC-bearing mice with the BTK inhibitor PCI32765 (ibrutinib) or by PI3Kgamma inhibition reprogrammed macrophages toward a T(H)1 phenotype that fostered CD8(+) T-cell cytotoxicity, and suppressed PDAC growth, indicating that BTK signaling mediates PDAC immunosuppression.	ibrutinib	54-62	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	238-241
26715645-7	2016	Inhibition of BTK with the FDA-approved inhibitor ibrutinib restores T cell-dependent antitumor immune responses to inhibit PDAC growth and improves responsiveness to chemotherapy, presenting a new therapeutic modality for pancreas cancer.	ibrutinib	50-59	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	14-17
26715645-4	2016	Treatment of PDAC-bearing mice with the BTK inhibitor PCI32765 (ibrutinib) or by PI3Kgamma inhibition reprogrammed macrophages toward a T(H)1 phenotype that fostered CD8(+) T-cell cytotoxicity, and suppressed PDAC growth, indicating that BTK signaling mediates PDAC immunosuppression.	ibrutinib	64-73	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	40-43
27076234-3	2016	Ibrutinib inhibits BTK in the BCR pathway and can be administered orally.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	19-22
26942591-11	2016	Off-study, we limit the use of ibrutinib to relapsed-refractory WM patients who harbor MYD88 mutations.	ibrutinib	31-40	MYD88 innate immune signal transduction adaptor	Homo sapiens	87-92
26139428-0	2016	Ibrutinib selectively targets FLT3-ITD in mutant FLT3-positive AML.	ibrutinib	0-9	fms related receptor tyrosine kinase 3	Homo sapiens	30-34
26139428-0	2016	Ibrutinib selectively targets FLT3-ITD in mutant FLT3-positive AML.	ibrutinib	0-9	fms related receptor tyrosine kinase 3	Homo sapiens	49-53
26588193-0	2016	beta2 -microglobulin normalization within 6 months of ibrutinib-based treatment is associated with superior progression-free survival in patients with chronic lymphocytic leukemia.	ibrutinib	54-63	beta-2-microglobulin	Homo sapiens	0-20
26588193-4	2016	RESULTS: B2M rapidly decreased during treatment with ibrutinib; on multivariable analysis, patients who received FCR (odds ratio, 0.40; 95% confidence interval [95% CI], 0.18-0.90 [P = .027]) were less likely to have normalized B2M at 6 months than patients treated with ibrutinib.	ibrutinib	53-62	beta-2-microglobulin	Homo sapiens	9-12
26588193-4	2016	RESULTS: B2M rapidly decreased during treatment with ibrutinib; on multivariable analysis, patients who received FCR (odds ratio, 0.40; 95% confidence interval [95% CI], 0.18-0.90 [P = .027]) were less likely to have normalized B2M at 6 months than patients treated with ibrutinib.	ibrutinib	53-62	beta-2-microglobulin	Homo sapiens	228-231
26588193-5	2016	On univariable analysis, normalization of B2M was associated with superior progression-free survival (PFS) from the 6-month landmark in patients treated with ibrutinib-based regimens and FCR.	ibrutinib	158-167	beta-2-microglobulin	Homo sapiens	42-45
26588193-6	2016	On multivariable analysis, failure to achieve normalized B2M at 6 months of treatment was associated with inferior PFS (hazard ratio, 16.9; 95% CI, 1.3-220.0 [P = .031]) for patients treated with ibrutinib, after adjusting for the effects of baseline B2M, stage of disease, fludarabine-refractory disease, and del(17p).	ibrutinib	196-205	beta-2-microglobulin	Homo sapiens	57-60
26588193-6	2016	On multivariable analysis, failure to achieve normalized B2M at 6 months of treatment was associated with inferior PFS (hazard ratio, 16.9; 95% CI, 1.3-220.0 [P = .031]) for patients treated with ibrutinib, after adjusting for the effects of baseline B2M, stage of disease, fludarabine-refractory disease, and del(17p).	ibrutinib	196-205	beta-2-microglobulin	Homo sapiens	251-254
26588193-8	2016	CONCLUSIONS: Normalization of B2M at 6 months in patients treated with ibrutinib was found to be a useful predictor of subsequent PFS and may assist in clinical decision-making.	ibrutinib	71-80	beta-2-microglobulin	Homo sapiens	30-33
26627823-0	2016	Analysis of the Effects of the Bruton"s tyrosine kinase (Btk) Inhibitor Ibrutinib on Monocyte Fcgamma Receptor (FcgammaR) Function.	ibrutinib	72-81	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	31-55
26822906-1	2016	Ibrutinib is a new-targeted therapy that irreversibly and specifically inhibits the Bruton"s Tyrosine Kinase (BTK), a key component of the signaling pathways of B cells.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	84-108
26822906-1	2016	Ibrutinib is a new-targeted therapy that irreversibly and specifically inhibits the Bruton"s Tyrosine Kinase (BTK), a key component of the signaling pathways of B cells.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	110-113
26775273-3	2016	Treatment paradigms including ibrutinib, a potent inhibitor of the BTK recently approved by the US Food and Drug Administration, have significantly improved disease outcome among high-risk and relapsed/refractory cases of chronic lymphocytic leukemia.	ibrutinib	30-39	Bruton tyrosine kinase	Homo sapiens	67-70
26701728-8	2016	Furthermore, pretreatment of CD69 high CLL cases with the B-cell receptor (BCR) pathway inhibitors ibrutinib and idelalisib decreased CD69 levels and enhanced bendamustine cytotoxic effect.	ibrutinib	99-108	CD69 molecule	Homo sapiens	29-33
26701728-8	2016	Furthermore, pretreatment of CD69 high CLL cases with the B-cell receptor (BCR) pathway inhibitors ibrutinib and idelalisib decreased CD69 levels and enhanced bendamustine cytotoxic effect.	ibrutinib	99-108	CD69 molecule	Homo sapiens	134-138
26627823-0	2016	Analysis of the Effects of the Bruton"s tyrosine kinase (Btk) Inhibitor Ibrutinib on Monocyte Fcgamma Receptor (FcgammaR) Function.	ibrutinib	72-81	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	57-60
26627823-1	2016	The irreversible Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib has shown efficacy against B-cell tumors such as chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma.	ibrutinib	58-67	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	17-41
26627823-1	2016	The irreversible Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib has shown efficacy against B-cell tumors such as chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma.	ibrutinib	58-67	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	43-46
26627823-11	2016	Pretreatment of monocytes with IFNgamma abrogated the effects of ibrutinib on FcgammaR-mediated cytokine production, suggesting that IFNgamma priming could overcome this Btk inhibition.	ibrutinib	65-74	interferon gamma	Mus musculus	31-39
26627823-11	2016	Pretreatment of monocytes with IFNgamma abrogated the effects of ibrutinib on FcgammaR-mediated cytokine production, suggesting that IFNgamma priming could overcome this Btk inhibition.	ibrutinib	65-74	interferon gamma	Mus musculus	133-141
26627823-11	2016	Pretreatment of monocytes with IFNgamma abrogated the effects of ibrutinib on FcgammaR-mediated cytokine production, suggesting that IFNgamma priming could overcome this Btk inhibition.	ibrutinib	65-74	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	170-173
26655421-0	2016	Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.	ibrutinib	0-9	IKAROS family zinc finger 2	Homo sapiens	186-192
26813987-2	2016	We report a serious side effect of ibrutinib potentially attributable to interaction with the moderate CYP3A4 inhibitor verapamil.	ibrutinib	35-44	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	103-109
26813987-9	2016	WHAT IS NEW AND CONCLUSION: This is the first description of a serious side effect of ibrutinib likely due to an interaction with the CYP3A4 inhibitor verapamil.	ibrutinib	86-95	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	134-140
26813987-10	2016	Prescriptions of ibrutinib must be carefully checked to identify possible interactions with CYP3A4 inhibitors and patients monitored accordingly.	ibrutinib	17-26	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	92-98
26655421-3	2016	We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton"s tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma.	ibrutinib	46-55	Bruton tyrosine kinase	Homo sapiens	87-111
26655421-3	2016	We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton"s tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma.	ibrutinib	46-55	Bruton tyrosine kinase	Homo sapiens	113-116
26540627-0	2016	Liquid chromatography-tandem mass spectrometric assay for the simultaneous determination of the irreversible BTK inhibitor ibrutinib and its dihydrodiol-metabolite in plasma and its application in mouse pharmacokinetic studies.	ibrutinib	123-132	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	109-112
26641137-1	2016	BACKGROUND: Irreversible inhibition of Bruton"s tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL).	ibrutinib	73-82	Bruton tyrosine kinase	Homo sapiens	39-63
26641137-1	2016	BACKGROUND: Irreversible inhibition of Bruton"s tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL).	ibrutinib	73-82	Bruton tyrosine kinase	Homo sapiens	65-68
26491071-6	2016	These translational responses were suppressed by inhibitors of BTK (ibrutinib) and SYK (tamatinib).	ibrutinib	68-77	Bruton tyrosine kinase	Homo sapiens	63-66
26717038-0	2016	Heightened BTK-dependent cell proliferation in unmutated chronic lymphocytic leukemia confers increased sensitivity to ibrutinib.	ibrutinib	119-128	Bruton tyrosine kinase	Homo sapiens	11-14
26841015-3	2016	Clinically, BTK inhibitors, specifically ibrutinib, have shown to be safe and effective on treating patients with indolent B-cell lymphomas and chronic lymphocytic leukemia (CLL).	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	12-15
26675335-6	2016	Ibrutinib, a covalent drug targeting the active site of BTK protein, was used as a model compound to demonstrate the feasibility of the workflow.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	56-59
26624983-0	2016	Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	109-112
26624983-1	2016	Targeting Bruton"s tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity.	ibrutinib	79-88	Bruton tyrosine kinase	Homo sapiens	10-34
26624983-1	2016	Targeting Bruton"s tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity.	ibrutinib	79-88	Bruton tyrosine kinase	Homo sapiens	36-39
26624983-1	2016	Targeting Bruton"s tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity.	ibrutinib	79-88	Bruton tyrosine kinase	Homo sapiens	65-68
26624983-4	2016	Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines.	ibrutinib	161-170	poly(ADP-ribose) glycohydrolase	Homo sapiens	76-107
26624983-4	2016	Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines.	ibrutinib	161-170	poly(ADP-ribose) glycohydrolase	Homo sapiens	109-113
26624983-7	2016	Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	54-57
26841018-5	2016	The combination of the Bruton tyrosine kinase inhibitor ibrutinib with an anti-CD20 antibody is an attractive option, because both drugs act synergistically: ibrutinib redistributes the CLL cells from their homing organs to the peripheral blood, and obinutuzumab eliminates the leukemic cells in the blood with particular efficiency.	ibrutinib	158-167	keratin 20	Homo sapiens	79-83
26362595-4	2016	Ibrutinib (PCI-32765) is a TKI of Bruton"s tyrosine kinase (Btk), a key kinase of the B-cell receptor signaling pathway that plays a significant role in the proliferation, differentiation and survival of B cells.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	34-58
26283682-0	2016	Interactions between Ibrutinib and Anti-CD20 Antibodies: Competing Effects on the Outcome of Combination Therapy.	ibrutinib	21-30	membrane spanning 4-domains A1	Homo sapiens	40-44
26283682-2	2016	Paradoxically, in preclinical studies, in vitro ibrutinib was reported to decrease CD20 expression and inhibit cellular effector mechanisms.	ibrutinib	48-57	membrane spanning 4-domains A1	Homo sapiens	83-87
26283682-6	2016	RESULTS: We demonstrate that CD20 expression on ibrutinib was rapidly and persistently downregulated (median reduction 74%, day 28, P &lt; 0.001) compared with baseline.	ibrutinib	48-57	membrane spanning 4-domains A1	Homo sapiens	29-33
26283682-9	2016	Ex vivo, tumor cells from patients on ibrutinib were less susceptible to anti-CD20 mAb-mediated complement-dependent cytotoxicity than pretreatment cells (median reduction 75%, P &lt; 0.001); however, opsonization by the complement protein C3d, which targets cells for phagocytosis, was relatively maintained.	ibrutinib	38-47	membrane spanning 4-domains A1	Homo sapiens	78-82
26283682-9	2016	Ex vivo, tumor cells from patients on ibrutinib were less susceptible to anti-CD20 mAb-mediated complement-dependent cytotoxicity than pretreatment cells (median reduction 75%, P &lt; 0.001); however, opsonization by the complement protein C3d, which targets cells for phagocytosis, was relatively maintained.	ibrutinib	38-47	endogenous retrovirus group K member 13	Homo sapiens	240-243
26283682-10	2016	Expression of decay-accelerating factor (CD55) decreased on ibrutinib, providing a likely mechanism for the preserved C3d opsonization.	ibrutinib	60-69	CD55 molecule (Cromer blood group)	Homo sapiens	41-45
26283682-12	2016	CONCLUSIONS: Our data indicate that ibrutinib promotes both positive and negative interactions with anti-CD20 mAbs, suggesting that successfully harnessing maximal antitumor effects of such combinations requires further investigation.	ibrutinib	36-45	membrane spanning 4-domains A1	Homo sapiens	105-109
26332019-6	2016	An increasing understanding of the disease biology has led to the development of targeted drugs for the treatment of CLL, such as the BTK inhibitor ibrutinib and PI3K inhibitor idelalisib.	ibrutinib	148-157	Bruton tyrosine kinase	Homo sapiens	134-137
26362595-4	2016	Ibrutinib (PCI-32765) is a TKI of Bruton"s tyrosine kinase (Btk), a key kinase of the B-cell receptor signaling pathway that plays a significant role in the proliferation, differentiation and survival of B cells.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	60-63
26362595-9	2016	In this article we review the inhibitory and immunomodulatory effects of ibrutinib in B-cell malignancies, autoimmune diseases and infections, as well as the communication between the Ror1 receptor tyrosine kinase and BCR and effects of ibrutinib on this crosstalk.	ibrutinib	237-246	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	184-188
26513168-7	2016	A better understanding of the BRAF/MEK/ERK pathway and the B-cell signaling pathway has allowed further exploration into the novel drugs vemurafenib, dabrafenib, trametinib, and ibrutinib.	ibrutinib	178-187	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	30-34
27980307-4	2016	Furthermore, some targeting drugs, such as lenalidomide, bortezomib and ibrutinib, directly or indirectly affect CD20 protein expression.	ibrutinib	72-81	keratin 20	Homo sapiens	113-117
26513168-7	2016	A better understanding of the BRAF/MEK/ERK pathway and the B-cell signaling pathway has allowed further exploration into the novel drugs vemurafenib, dabrafenib, trametinib, and ibrutinib.	ibrutinib	178-187	mitogen-activated protein kinase kinase 7	Homo sapiens	35-38
26513168-7	2016	A better understanding of the BRAF/MEK/ERK pathway and the B-cell signaling pathway has allowed further exploration into the novel drugs vemurafenib, dabrafenib, trametinib, and ibrutinib.	ibrutinib	178-187	mitogen-activated protein kinase 1	Homo sapiens	39-42
26440741-0	2016	Preclinical combination of TP-0903, an AXL inhibitor and B-PAC-1, a procaspase-activating compound with ibrutinib in chronic lymphocytic leukemia.	ibrutinib	104-113	dual specificity phosphatase 2	Homo sapiens	59-64
26174628-8	2016	Finally, treatment of ibrutinib-sensitive and -resistant patient-derived MCLs with ON123300 also triggered apoptosis and inhibition of the Rb and PI3K/AKT pathways, suggesting that this compound might be an effective agent in MCL, including ibrutinib-resistant forms of the disease.	ibrutinib	22-31	RB transcriptional corepressor 1	Homo sapiens	139-141
27246223-1	2016	To evaluate the antiproliferative activity of a novel BET Bromodomain inhibitor as single agent and in combination with the BTK inhibitor ibrutinib in non-Hodgkin lymphoma cell lines, we performed the MTT proliferation assay.	ibrutinib	138-147	Bruton tyrosine kinase	Homo sapiens	124-127
26174628-8	2016	Finally, treatment of ibrutinib-sensitive and -resistant patient-derived MCLs with ON123300 also triggered apoptosis and inhibition of the Rb and PI3K/AKT pathways, suggesting that this compound might be an effective agent in MCL, including ibrutinib-resistant forms of the disease.	ibrutinib	22-31	AKT serine/threonine kinase 1	Homo sapiens	151-154
26788279-5	2015	Cutaneous and systemic relapses responded well to immunomodulatory therapy with lenalidomide followed by Bruton"s tyrosine kinase inhibition with ibrutinib.	ibrutinib	146-155	Bruton tyrosine kinase	Homo sapiens	105-129
26699656-0	2016	CD79B limits response of diffuse large B cell lymphoma to ibrutinib.	ibrutinib	58-67	CD79b molecule	Homo sapiens	0-5
26699656-3	2016	In the current study, cDNA microarray and Western blot analyses revealed CD79B upregulation in the activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) that display differential resistance to ibrutinib.	ibrutinib	203-212	CD79b molecule	Homo sapiens	73-78
26699656-4	2016	CD79B overexpression was sufficient to induce resistance to ibrutinib and enhanced AKT and MAPK activation, indicative of an alternative mechanism underlying resistance.	ibrutinib	60-69	CD79b molecule	Homo sapiens	0-5
26699656-5	2016	Conversely, depletion of CD79B sensitized primary refractory cells to ibrutinib and led to reduced phosphorylation of AKT or MAPK.	ibrutinib	70-79	CD79b molecule	Homo sapiens	25-30
26699656-7	2016	Our data collectively indicate that CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib.	ibrutinib	135-144	CD79b molecule	Homo sapiens	36-41
26699656-7	2016	Our data collectively indicate that CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib.	ibrutinib	135-144	AKT serine/threonine kinase 1	Homo sapiens	82-85
26699656-7	2016	Our data collectively indicate that CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib.	ibrutinib	255-264	CD79b molecule	Homo sapiens	36-41
26699656-7	2016	Our data collectively indicate that CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib.	ibrutinib	255-264	AKT serine/threonine kinase 1	Homo sapiens	82-85
26890007-4	2016	However, the recently approved BTK and PI3K inhibitors ibrutinib and idelalisib have the best efficacy ever documented in patients with these high-risk genomic alterations and/or refractory CLL.	ibrutinib	55-64	Bruton tyrosine kinase	Homo sapiens	31-34
26630553-2	2015	On the basis of the structure of PCI-32765 (ibrutinib), a BTK kinase inhibitor that was recently reported to bear FLT3 kinase activity through a structure-guided drug design approach, we have discovered compound 18 (CHMFL-FLT3-122), which displayed an IC50 of 40 nM against FLT3 kinase and achieved selectivity over BTK kinase (over 10-fold).	ibrutinib	44-53	fms related receptor tyrosine kinase 3	Homo sapiens	114-118
26630553-2	2015	On the basis of the structure of PCI-32765 (ibrutinib), a BTK kinase inhibitor that was recently reported to bear FLT3 kinase activity through a structure-guided drug design approach, we have discovered compound 18 (CHMFL-FLT3-122), which displayed an IC50 of 40 nM against FLT3 kinase and achieved selectivity over BTK kinase (over 10-fold).	ibrutinib	44-53	fms related receptor tyrosine kinase 3	Homo sapiens	222-226
26630553-2	2015	On the basis of the structure of PCI-32765 (ibrutinib), a BTK kinase inhibitor that was recently reported to bear FLT3 kinase activity through a structure-guided drug design approach, we have discovered compound 18 (CHMFL-FLT3-122), which displayed an IC50 of 40 nM against FLT3 kinase and achieved selectivity over BTK kinase (over 10-fold).	ibrutinib	44-53	fms related receptor tyrosine kinase 3	Homo sapiens	222-226
26337493-2	2015	Ibrutinib, a covalent inhibitor of Bruton tyrosine kinase (BTK), inhibits B-cell receptor signaling and is an effective, US Food and Drug Administration (FDA)-approved treatment of CLL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	35-57
26788133-6	2015	Ibrutinib, an oral irreversible BTK inhibitor, has emerged as a promising targeted therapy for patients with B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	32-35
26540570-2	2015	Inhibition of BTK by Ibrutinib has been shown to kill ABC DLBCL cells that carry activating mutations in the BCR adaptor CD79.	ibrutinib	21-30	Bruton tyrosine kinase	Homo sapiens	14-17
26540570-3	2015	However, mutations in BTK or in downstream components such as CARMA1/CARD11 can render lymphomas Ibrutinib resistant.	ibrutinib	97-106	Bruton tyrosine kinase	Homo sapiens	22-25
26540570-3	2015	However, mutations in BTK or in downstream components such as CARMA1/CARD11 can render lymphomas Ibrutinib resistant.	ibrutinib	97-106	caspase recruitment domain family member 11	Homo sapiens	62-68
26540570-3	2015	However, mutations in BTK or in downstream components such as CARMA1/CARD11 can render lymphomas Ibrutinib resistant.	ibrutinib	97-106	caspase recruitment domain family member 11	Homo sapiens	69-75
26540570-6	2015	Combined inhibition of BTK by Ibrutinib and MALT1 by S-Mepazine additively impaired MALT1 cleavage activity and expression of NF-kappaB pro-survival factors.	ibrutinib	30-39	Bruton tyrosine kinase	Homo sapiens	23-26
26540570-6	2015	Combined inhibition of BTK by Ibrutinib and MALT1 by S-Mepazine additively impaired MALT1 cleavage activity and expression of NF-kappaB pro-survival factors.	ibrutinib	30-39	MALT1 paracaspase	Homo sapiens	84-89
26540570-8	2015	Moreover, while expression of oncogenic CARMA1 in CD79 mutant cells conferred Ibrutinib resistance, double mutant cells were still sensitive to MALT1 inhibition by S-Mepazine.	ibrutinib	78-87	caspase recruitment domain family member 11	Homo sapiens	40-46
26637884-2	2015	This study investigated the combination effect of bendamustine and the Bruton tyrosine kinase (BTK) inhibitor PCI-32765 on MCL cell death and the underlying mechanisms.	ibrutinib	110-119	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	71-93
26637884-2	2015	This study investigated the combination effect of bendamustine and the Bruton tyrosine kinase (BTK) inhibitor PCI-32765 on MCL cell death and the underlying mechanisms.	ibrutinib	110-119	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	95-98
26628631-6	2015	Ibrutinib, a covalent inhibitor of Bruton"s tyrosine kinase, and idelalisib, a selective inhibitor of PI3Kdelta, have obtained regulatory approval in chronic lymphocytic leukemia.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	35-59
26628631-7	2015	Ibrutinib and idelalisib are active in patients with high-risk features, achieving superior disease control in difficult-to-treat patients than prior best therapy, making them the preferred agents for chronic lymphocytic leukemia with TP53 aberrations and for patients resistant to chemoimmunotherapy.	ibrutinib	0-9	tumor protein p53	Homo sapiens	235-239
26337493-2	2015	Ibrutinib, a covalent inhibitor of Bruton tyrosine kinase (BTK), inhibits B-cell receptor signaling and is an effective, US Food and Drug Administration (FDA)-approved treatment of CLL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	59-62
26089373-0	2015	Treatment with Ibrutinib Inhibits BTK- and VLA-4-Dependent Adhesion of Chronic Lymphocytic Leukemia Cells In Vivo.	ibrutinib	15-24	Bruton tyrosine kinase	Homo sapiens	34-37
26359510-7	2015	When ibrutinib was combined with the P2Y12 inhibitor, cangrelor, thrombus formation under arterial shear was inhibited additively.	ibrutinib	5-14	purinergic receptor P2Y12	Homo sapiens	37-42
26359510-8	2015	CONCLUSIONS: These findings suggest that (1) ibrutinib causes GPVI and integrin alphaIIbbeta3 platelet signaling deficiencies that result in formation of unstable thrombi and may contribute toward bleeding observed in vivo and (2) combining ibrutinib with P2Y12 antagonists, which also inhibit thrombus stability, may have a detrimental effect on hemostasis.	ibrutinib	45-54	glycoprotein VI platelet	Homo sapiens	62-66
26359510-8	2015	CONCLUSIONS: These findings suggest that (1) ibrutinib causes GPVI and integrin alphaIIbbeta3 platelet signaling deficiencies that result in formation of unstable thrombi and may contribute toward bleeding observed in vivo and (2) combining ibrutinib with P2Y12 antagonists, which also inhibit thrombus stability, may have a detrimental effect on hemostasis.	ibrutinib	45-54	purinergic receptor P2Y12	Homo sapiens	256-261
26194765-5	2015	The SYK inhibitor (tamatinib) or the BTK inhibitor (ibrutinib) each blocked phosphorylation.	ibrutinib	52-61	Bruton tyrosine kinase	Homo sapiens	37-40
26089373-7	2015	Stimulation of CLL cells from patients on ibrutinib with PMA, which activates PKC independent of BTK, restored the ability of the cells to adhere to fibronectin in a VLA-4-dependent manner.	ibrutinib	42-51	Bruton tyrosine kinase	Homo sapiens	97-100
26089373-7	2015	Stimulation of CLL cells from patients on ibrutinib with PMA, which activates PKC independent of BTK, restored the ability of the cells to adhere to fibronectin in a VLA-4-dependent manner.	ibrutinib	42-51	fibronectin 1	Homo sapiens	149-160
26089373-8	2015	Finally, the addition of ibrutinib to CLL cells adhered to fibronectin in vitro caused the detachment of 17% of the cells, on average; consisten t with in vivo observations of an increasing lymphocytosis within 4 hours of starting ibrutinib.	ibrutinib	25-34	fibronectin 1	Homo sapiens	59-70
26089373-8	2015	Finally, the addition of ibrutinib to CLL cells adhered to fibronectin in vitro caused the detachment of 17% of the cells, on average; consisten t with in vivo observations of an increasing lymphocytosis within 4 hours of starting ibrutinib.	ibrutinib	231-240	fibronectin 1	Homo sapiens	59-70
26284584-3	2015	The constitutive MDR phenotype of IGHV unmutated cells was partially dependent on B cell receptor signaling, as shown by the inhibitory effect exerted by ibrutinib.	ibrutinib	154-163	immunoglobulin heavy variable 3/OR16-17 (non-functional)	Homo sapiens	34-38
26282174-7	2015	We further provide evidence that ibrutinib, a Btk inhibitor that promotes mobilization of leukemic cells from SLOs, normalizes the imbalance between CXCR4/CCR7 and S1P1.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	46-49
26282174-7	2015	We further provide evidence that ibrutinib, a Btk inhibitor that promotes mobilization of leukemic cells from SLOs, normalizes the imbalance between CXCR4/CCR7 and S1P1.	ibrutinib	33-42	C-X-C motif chemokine receptor 4	Homo sapiens	149-154
26282174-7	2015	We further provide evidence that ibrutinib, a Btk inhibitor that promotes mobilization of leukemic cells from SLOs, normalizes the imbalance between CXCR4/CCR7 and S1P1.	ibrutinib	33-42	C-C motif chemokine receptor 7	Homo sapiens	155-159
26282174-7	2015	We further provide evidence that ibrutinib, a Btk inhibitor that promotes mobilization of leukemic cells from SLOs, normalizes the imbalance between CXCR4/CCR7 and S1P1.	ibrutinib	33-42	sphingosine-1-phosphate receptor 1	Homo sapiens	164-168
26138997-3	2015	Ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, is the first drug approved specifically for WM by the FDA after a clinical trial showed impressive response in previously treated WM.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	19-41
26429964-1	2015	In this issue of Blood, Bernard et al provide evidence that ibrutinib, the orally administered inhibitor of Bruton tyrosine kinase (BTK), crosses the blood-brain barrier and has activity against mantle cell lymphoma (MCL) in the central nervous system (CNS).	ibrutinib	60-69	Bruton tyrosine kinase	Homo sapiens	108-130
26429964-1	2015	In this issue of Blood, Bernard et al provide evidence that ibrutinib, the orally administered inhibitor of Bruton tyrosine kinase (BTK), crosses the blood-brain barrier and has activity against mantle cell lymphoma (MCL) in the central nervous system (CNS).	ibrutinib	60-69	Bruton tyrosine kinase	Homo sapiens	132-135
26138997-3	2015	Ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, is the first drug approved specifically for WM by the FDA after a clinical trial showed impressive response in previously treated WM.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	43-46
26138997-5	2015	With identification of novel genetic mutations impacting response to ibrutinib, it would be possible to individualize therapy based on MYD88 and CXCR4 genotypes.	ibrutinib	69-78	MYD88 innate immune signal transduction adaptor	Homo sapiens	135-140
26138997-5	2015	With identification of novel genetic mutations impacting response to ibrutinib, it would be possible to individualize therapy based on MYD88 and CXCR4 genotypes.	ibrutinib	69-78	C-X-C motif chemokine receptor 4	Homo sapiens	145-150
26458447-5	2015	A Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has also been reported as a promising agent.	ibrutinib	42-51	Bruton tyrosine kinase	Homo sapiens	2-24
26458447-5	2015	A Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has also been reported as a promising agent.	ibrutinib	42-51	Bruton tyrosine kinase	Homo sapiens	26-29
26317541-5	2015	Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP3 Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP3R interaction and thus inducing Ca2+-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton"s tyrosine kinase inhibitor Ibrutinib.	ibrutinib	383-392	BCL2 apoptosis regulator	Homo sapiens	59-64
26317541-5	2015	Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP3 Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP3R interaction and thus inducing Ca2+-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton"s tyrosine kinase inhibitor Ibrutinib.	ibrutinib	383-392	BCL2 apoptosis regulator	Homo sapiens	147-152
26317541-5	2015	Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP3 Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP3R interaction and thus inducing Ca2+-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton"s tyrosine kinase inhibitor Ibrutinib.	ibrutinib	383-392	inositol 1,4,5-trisphosphate receptor type 3	Homo sapiens	153-157
26254443-0	2015	Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib.	ibrutinib	122-131	delta/notch-like EGF repeat containing	Mus musculus	24-27
27358886-7	2015	Recent clinical trials with ibrutinib (Bruton"s Tyrosine Kinase inhibitor) and temsirolimus (mTOR inhibitor) have shown excellent efficacies in the treatment of MCL.	ibrutinib	28-37	Bruton tyrosine kinase	Homo sapiens	39-63
26254443-5	2015	Cotreatment with BA and the BTK inhibitor ibrutinib synergistically induces apoptosis of MCL cells.	ibrutinib	42-51	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	28-31
26254443-7	2015	BA treatment also induced apoptosis of the in vitro isolated, ibrutinib-resistant MCL cells, which overexpress CDK6, BCL2, Bcl-xL, XIAP, and AKT, but lack ibrutinib resistance-conferring BTK mutation.	ibrutinib	62-71	cyclin-dependent kinase 6	Mus musculus	111-115
26068951-7	2015	Importantly, we show an enhanced antitumor effect of sudemycin in combination with ibrutinib that might be related to the modulation of the alternative splicing of the inhibitor of Btk (IBTK).	ibrutinib	83-92	Bruton tyrosine kinase	Homo sapiens	181-184
26068951-7	2015	Importantly, we show an enhanced antitumor effect of sudemycin in combination with ibrutinib that might be related to the modulation of the alternative splicing of the inhibitor of Btk (IBTK).	ibrutinib	83-92	inhibitor of Bruton tyrosine kinase	Homo sapiens	186-190
26111359-1	2015	Ibrutinib (Imbruvica ) is an irreversible, potent inhibitor of Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	63-87
26348529-0	2015	Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice.	ibrutinib	31-40	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	14-17
26348529-0	2015	Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice.	ibrutinib	31-40	IL2 inducible T cell kinase	Mus musculus	22-25
26348529-2	2015	Ibrutinib is an FDA-approved potent inhibitor of both BTK and ITK that impairs B-cell and T-cell function.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	54-57
26348529-2	2015	Ibrutinib is an FDA-approved potent inhibitor of both BTK and ITK that impairs B-cell and T-cell function.	ibrutinib	0-9	IL2 inducible T cell kinase	Mus musculus	62-65
26223732-3	2015	Ibrutinib, formerly PCI-32765, is a first in class, potent, specific, irreversible and relatively safe BTK inhibitor, demonstrating so far an impressive efficacy in the treatment of chronic lymphocytic leukemia, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma (MCL), Waldenstrom macroglobulinemia and multiple myeloma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	103-106
26111359-1	2015	Ibrutinib (Imbruvica ) is an irreversible, potent inhibitor of Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	89-92
26111359-1	2015	Ibrutinib (Imbruvica ) is an irreversible, potent inhibitor of Bruton"s tyrosine kinase (BTK).	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	63-87
26111359-1	2015	Ibrutinib (Imbruvica ) is an irreversible, potent inhibitor of Bruton"s tyrosine kinase (BTK).	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	89-92
26111359-5	2015	In certain cases, the outcome of ibrutinib treatment likely results from the combined inhibition of BTK and other kinases, causing additive or synergistic, effects.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	100-103
26017814-6	2015	This agent (Ibrutinib-SiR-COOH) is expected to be a valuable chemical tool in deciphering Btk biology in cancer and host cells in vivo.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	90-93
26292723-5	2015	Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines.	ibrutinib	82-91	fms related receptor tyrosine kinase 3	Homo sapiens	18-22
26292723-5	2015	Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines.	ibrutinib	82-91	Bruton tyrosine kinase	Homo sapiens	39-42
26292723-5	2015	Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines.	ibrutinib	82-91	Bruton tyrosine kinase	Homo sapiens	68-71
26292723-6	2015	Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5.	ibrutinib	12-21	AKT serine/threonine kinase 1	Homo sapiens	84-87
25829398-1	2015	PURPOSE: Bruton"s tyrosine kinase (BTK) is a critical enzyme in the B-cell receptor pathway and is inhibited by ibrutinib due to covalent binding to the kinase domain.	ibrutinib	112-121	Bruton tyrosine kinase	Homo sapiens	9-33
26292723-6	2015	Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5.	ibrutinib	12-21	signal transducer and activator of transcription 5A	Homo sapiens	92-97
26292723-8	2015	Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival.	ibrutinib	23-32	fms related receptor tyrosine kinase 3	Homo sapiens	78-82
26292723-9	2015	These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML.	ibrutinib	42-51	fms related receptor tyrosine kinase 3	Homo sapiens	69-73
26285204-5	2015	We demonstrated that Mino/FR were highly cross-resistant to other antinucleosides (cytarabine, cladribine, gemcitabine) and to an inhibitor of Bruton tyrosine kinase (BTK) ibrutinib.	ibrutinib	172-181	Bruton tyrosine kinase	Homo sapiens	143-165
26285204-5	2015	We demonstrated that Mino/FR were highly cross-resistant to other antinucleosides (cytarabine, cladribine, gemcitabine) and to an inhibitor of Bruton tyrosine kinase (BTK) ibrutinib.	ibrutinib	172-181	Bruton tyrosine kinase	Homo sapiens	167-170
26327780-6	2015	The Btk inhibitor ibrutinib has been approved for the treatment of chronic lymphocytic leukemia and mantle-cell lymphoma recently.	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
25829398-1	2015	PURPOSE: Bruton"s tyrosine kinase (BTK) is a critical enzyme in the B-cell receptor pathway and is inhibited by ibrutinib due to covalent binding to the kinase domain.	ibrutinib	112-121	Bruton tyrosine kinase	Homo sapiens	35-38
25829398-10	2015	Serial samples of CLL cells obtained before and 2, 4, 12, or 36 weeks after the start of ibrutinib showed inhibition of BTK activity and sensitivity to ABTs.	ibrutinib	89-98	Bruton tyrosine kinase	Homo sapiens	120-123
25829398-11	2015	Among the three BCL-2 family antiapoptotic proteins that are overexpressed in CLL, levels of MCL-1 and BCL-XL were decreased after ibrutinib while ABT-199 selectively antagonizes BCL-2.	ibrutinib	131-140	BCL2 apoptosis regulator	Homo sapiens	16-21
25829398-11	2015	Among the three BCL-2 family antiapoptotic proteins that are overexpressed in CLL, levels of MCL-1 and BCL-XL were decreased after ibrutinib while ABT-199 selectively antagonizes BCL-2.	ibrutinib	131-140	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	93-98
25829398-11	2015	Among the three BCL-2 family antiapoptotic proteins that are overexpressed in CLL, levels of MCL-1 and BCL-XL were decreased after ibrutinib while ABT-199 selectively antagonizes BCL-2.	ibrutinib	131-140	BCL2 like 1	Homo sapiens	103-109
25858358-2	2015	Ibrutinib is an orally bioavailable and highly specific BTK inhibitor that was recently approved for treatment of patients with recurrent CLL and mantle cell lymphoma (MCL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	56-59
26275952-3	2015	Ibrutinib is a first-in-class Bruton"s tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	30-54
26275952-3	2015	Ibrutinib is a first-in-class Bruton"s tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	56-59
26116658-0	2015	Safety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 study.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	23-26
26099967-0	2015	The novel beta2-selective proteasome inhibitor LU-102 decreases phosphorylation of I kappa B and induces highly synergistic cytotoxicity in combination with ibrutinib in multiple myeloma cells.	ibrutinib	157-166	potassium calcium-activated channel subfamily M regulatory beta subunit 2	Homo sapiens	10-15
26099967-6	2015	However, bortezomib induces phosphorylation of IkappaB and activation of NF-kappaB in MM cells, while ibrutinib inhibits the IkappaB/NF-kappaB axis, suggesting antagonistic signaling.	ibrutinib	102-111	nuclear factor kappa B subunit 1	Homo sapiens	133-142
25944695-2	2015	Recently, several drugs that target the BCR signaling pathway, especially the Btk inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicates that pharmacological inhibition of BCR pathway holds promise in B-cell lymphoma treatment.	ibrutinib	92-101	Bruton tyrosine kinase	Homo sapiens	78-81
26193343-3	2015	We hypothesized that ABC, but not GCB, DLBCL tumors would respond to ibrutinib, an inhibitor of BCR signaling.	ibrutinib	69-78	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	21-24
26193343-4	2015	In a phase 1/2 clinical trial that involved 80 subjects with relapsed or refractory DLBCL, ibrutinib produced complete or partial responses in 37% (14/38) of those with ABC DLBCL, but in only 5% (1/20) of subjects with GCB DLBCL (P = 0.0106).	ibrutinib	91-100	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	169-172
26193343-5	2015	ABC tumors with BCR mutations responded to ibrutinib frequently (5/9; 55.5%), especially those with concomitant myeloid differentiation primary response 88 (MYD88) mutations (4/5; 80%), a result that is consistent with in vitro cooperation between the BCR and MYD88 pathways.	ibrutinib	43-52	MYD88 innate immune signal transduction adaptor	Homo sapiens	260-265
26193343-7	2015	These results support the selective development of ibrutinib for the treatment of ABC DLBCL.	ibrutinib	51-60	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	82-85
26171235-0	2015	Effect of CYP3A perpetrators on ibrutinib exposure in healthy participants.	ibrutinib	32-41	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	10-15
26171235-2	2015	Given the prominent role of CYP3A in ibrutinib metabolism, effect of coadministration of CYP3A perpetrators with ibrutinib was evaluated in healthy adults.	ibrutinib	113-122	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	89-94
26170206-6	2015	B cell-targeted agents such as the Bruton"s tyrosine kinase inhibitor ibrutinib and the phosphatidylinositol 3-kinase inhibitor idelalisib are the first of a new generation of oral agents for CLL.	ibrutinib	70-79	Bruton tyrosine kinase	Homo sapiens	35-59
25582069-0	2015	The BCL2 antagonist ABT-199 triggers apoptosis, and augments ibrutinib and idelalisib mediated cytotoxicity in CXCR4 Wild-type and CXCR4 WHIM mutated Waldenstrom macroglobulinaemia cells.	ibrutinib	61-70	BCL2 apoptosis regulator	Homo sapiens	4-8
25972157-0	2015	Hypermorphic mutation of phospholipase C, gamma2 acquired in ibrutinib-resistant CLL confers BTK independency upon B-cell receptor activation.	ibrutinib	61-70	phospholipase C gamma 2	Homo sapiens	25-48
25972157-0	2015	Hypermorphic mutation of phospholipase C, gamma2 acquired in ibrutinib-resistant CLL confers BTK independency upon B-cell receptor activation.	ibrutinib	61-70	Bruton tyrosine kinase	Homo sapiens	93-96
25972157-2	2015	Recent reports attribute ibrutinib resistance to acquired mutations in Bruton agammaglobulinemia tyrosine kinase (BTK), the target of ibrutinib, as well as the immediate downstream effector phospholipase C, gamma2 (PLCG2).	ibrutinib	25-34	Bruton tyrosine kinase	Homo sapiens	71-112
25972157-2	2015	Recent reports attribute ibrutinib resistance to acquired mutations in Bruton agammaglobulinemia tyrosine kinase (BTK), the target of ibrutinib, as well as the immediate downstream effector phospholipase C, gamma2 (PLCG2).	ibrutinib	25-34	Bruton tyrosine kinase	Homo sapiens	114-117
25972157-2	2015	Recent reports attribute ibrutinib resistance to acquired mutations in Bruton agammaglobulinemia tyrosine kinase (BTK), the target of ibrutinib, as well as the immediate downstream effector phospholipase C, gamma2 (PLCG2).	ibrutinib	25-34	phospholipase C gamma 2	Homo sapiens	215-220
25972157-2	2015	Recent reports attribute ibrutinib resistance to acquired mutations in Bruton agammaglobulinemia tyrosine kinase (BTK), the target of ibrutinib, as well as the immediate downstream effector phospholipase C, gamma2 (PLCG2).	ibrutinib	134-143	Bruton tyrosine kinase	Homo sapiens	71-112
25972157-2	2015	Recent reports attribute ibrutinib resistance to acquired mutations in Bruton agammaglobulinemia tyrosine kinase (BTK), the target of ibrutinib, as well as the immediate downstream effector phospholipase C, gamma2 (PLCG2).	ibrutinib	134-143	Bruton tyrosine kinase	Homo sapiens	114-117
25972157-3	2015	Although the C481S mutation found in BTK has been shown to disable ibrutinib"s capacity to irreversibly bind this primary target, the detailed mechanisms of mutations in PLCG2 have yet to be established.	ibrutinib	67-76	Bruton tyrosine kinase	Homo sapiens	37-40
25972157-3	2015	Although the C481S mutation found in BTK has been shown to disable ibrutinib"s capacity to irreversibly bind this primary target, the detailed mechanisms of mutations in PLCG2 have yet to be established.	ibrutinib	67-76	phospholipase C gamma 2	Homo sapiens	170-175
25972157-4	2015	Herein, we characterize the enhanced signaling competence, BTK independence, and surface immunoglobulin dependence of the PLCG2 mutation at R665W, which has been documented in ibrutinib-resistant CLL.	ibrutinib	176-185	Bruton tyrosine kinase	Homo sapiens	59-62
25972157-4	2015	Herein, we characterize the enhanced signaling competence, BTK independence, and surface immunoglobulin dependence of the PLCG2 mutation at R665W, which has been documented in ibrutinib-resistant CLL.	ibrutinib	176-185	phospholipase C gamma 2	Homo sapiens	122-127
25972157-7	2015	Our studies reveal that proximal kinases SYK and LYN are critical for the activation of mutant PLCG2 and that therapeutics targeting SYK and LYN can combat molecular resistance in cell line models and primary CLL cells from ibrutinib-resistant patients.	ibrutinib	224-233	spleen associated tyrosine kinase	Homo sapiens	41-44
25972157-7	2015	Our studies reveal that proximal kinases SYK and LYN are critical for the activation of mutant PLCG2 and that therapeutics targeting SYK and LYN can combat molecular resistance in cell line models and primary CLL cells from ibrutinib-resistant patients.	ibrutinib	224-233	LYN proto-oncogene, Src family tyrosine kinase	Homo sapiens	49-52
25972157-7	2015	Our studies reveal that proximal kinases SYK and LYN are critical for the activation of mutant PLCG2 and that therapeutics targeting SYK and LYN can combat molecular resistance in cell line models and primary CLL cells from ibrutinib-resistant patients.	ibrutinib	224-233	phospholipase C gamma 2	Homo sapiens	95-100
25972157-7	2015	Our studies reveal that proximal kinases SYK and LYN are critical for the activation of mutant PLCG2 and that therapeutics targeting SYK and LYN can combat molecular resistance in cell line models and primary CLL cells from ibrutinib-resistant patients.	ibrutinib	224-233	spleen associated tyrosine kinase	Homo sapiens	133-136
25972157-7	2015	Our studies reveal that proximal kinases SYK and LYN are critical for the activation of mutant PLCG2 and that therapeutics targeting SYK and LYN can combat molecular resistance in cell line models and primary CLL cells from ibrutinib-resistant patients.	ibrutinib	224-233	LYN proto-oncogene, Src family tyrosine kinase	Homo sapiens	141-144
25972157-8	2015	Altogether, our results engender a molecular understanding of the identified aberration at PLCG2 and explore its functional dependency on BTK, SYK, and LYN, suggesting alternative strategies to combat acquired ibrutinib resistance.	ibrutinib	210-219	phospholipase C gamma 2	Homo sapiens	91-96
25972157-8	2015	Altogether, our results engender a molecular understanding of the identified aberration at PLCG2 and explore its functional dependency on BTK, SYK, and LYN, suggesting alternative strategies to combat acquired ibrutinib resistance.	ibrutinib	210-219	Bruton tyrosine kinase	Homo sapiens	138-141
25972157-8	2015	Altogether, our results engender a molecular understanding of the identified aberration at PLCG2 and explore its functional dependency on BTK, SYK, and LYN, suggesting alternative strategies to combat acquired ibrutinib resistance.	ibrutinib	210-219	spleen associated tyrosine kinase	Homo sapiens	143-146
25972157-8	2015	Altogether, our results engender a molecular understanding of the identified aberration at PLCG2 and explore its functional dependency on BTK, SYK, and LYN, suggesting alternative strategies to combat acquired ibrutinib resistance.	ibrutinib	210-219	LYN proto-oncogene, Src family tyrosine kinase	Homo sapiens	152-155
25522014-0	2015	Trisomy 12 is associated with an abbreviated redistribution lymphocytosis during treatment with the BTK inhibitor ibrutinib in patients with chronic lymphocytic leukaemia.	ibrutinib	114-123	Bruton tyrosine kinase	Homo sapiens	100-103
25944695-3	2015	Here we present a novel covalent irreversible Btk inhibitor PLS-123 with more potent anti-proliferative activity compared with ibrutinib in multiple cellular and in vivo models through effective apoptosis induction and dual-action inhibitory mode of Btk activation.	ibrutinib	127-136	Bruton tyrosine kinase	Homo sapiens	46-49
25944695-4	2015	The phosphorylation of BCR downstream activating AKT/mTOR and MAPK signal pathways was also more significantly reduced after treatment with PLS-123 than ibrutinib.	ibrutinib	153-162	AKT serine/threonine kinase 1	Homo sapiens	49-52
25944695-4	2015	The phosphorylation of BCR downstream activating AKT/mTOR and MAPK signal pathways was also more significantly reduced after treatment with PLS-123 than ibrutinib.	ibrutinib	153-162	mechanistic target of rapamycin kinase	Homo sapiens	53-57
25388373-2	2015	Significant progress in MCL treatment is achieved through therapies targeting BCR-associated kinases, i.e., Ibrutinib and Fostamatinib, inhibitors of BTK and SYK, respectively.	ibrutinib	108-117	Bruton tyrosine kinase	Homo sapiens	150-153
25388373-2	2015	Significant progress in MCL treatment is achieved through therapies targeting BCR-associated kinases, i.e., Ibrutinib and Fostamatinib, inhibitors of BTK and SYK, respectively.	ibrutinib	108-117	spleen associated tyrosine kinase	Homo sapiens	158-161
26022368-2	2015	In particular, ibrutinib, previously called PCI-32765, is a potent inhibitor of Bruton tyrosine kinase (Btk), recently approved for the treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).	ibrutinib	15-24	Bruton tyrosine kinase	Homo sapiens	80-102
25388373-7	2015	Specific inhibition of BTK by Ibrutinib or SYK by Fostamatinib (R406) reversed these protective effects and decreased both basal and BCR-induced autocrine cytokine secretions associated with STAT3 phosphorylation.	ibrutinib	30-39	Bruton tyrosine kinase	Homo sapiens	23-26
25388373-7	2015	Specific inhibition of BTK by Ibrutinib or SYK by Fostamatinib (R406) reversed these protective effects and decreased both basal and BCR-induced autocrine cytokine secretions associated with STAT3 phosphorylation.	ibrutinib	30-39	signal transducer and activator of transcription 3	Homo sapiens	191-196
26059659-5	2015	The FDA-approved BTK inhibitor ibrutinib (PCI-32765) efficiently suppresses infarct volume growth and neurological damage in a brain ischaemia/reperfusion model in mice.	ibrutinib	31-40	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	17-20
26059659-6	2015	Ibrutinib inhibits maturation of IL-1beta by suppressing caspase-1 activation in infiltrating macrophages and neutrophils in the infarcted area of ischaemic brain.	ibrutinib	0-9	interleukin 1 beta	Mus musculus	33-41
26059659-6	2015	Ibrutinib inhibits maturation of IL-1beta by suppressing caspase-1 activation in infiltrating macrophages and neutrophils in the infarcted area of ischaemic brain.	ibrutinib	0-9	caspase 1	Mus musculus	57-66
26048374-7	2015	RESULTS: We showed that MCL-ICs are resistant to genotoxic agents vincristine, doxorubicin, and the newly approved Burton tyrosine kinase (BTK) inhibitor ibrutinib.	ibrutinib	154-163	Bruton tyrosine kinase	Homo sapiens	115-137
26048374-7	2015	RESULTS: We showed that MCL-ICs are resistant to genotoxic agents vincristine, doxorubicin, and the newly approved Burton tyrosine kinase (BTK) inhibitor ibrutinib.	ibrutinib	154-163	Bruton tyrosine kinase	Homo sapiens	139-142
26118882-1	2015	Ibrutinib (Imbruvica ) is a first-in-class, orally administered once-daily, that inhibits B-cell antigen receptor signaling downstream of Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	138-162
26118882-1	2015	Ibrutinib (Imbruvica ) is a first-in-class, orally administered once-daily, that inhibits B-cell antigen receptor signaling downstream of Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	164-167
26118882-1	2015	Ibrutinib (Imbruvica ) is a first-in-class, orally administered once-daily, that inhibits B-cell antigen receptor signaling downstream of Bruton"s tyrosine kinase (BTK).	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	138-162
26118882-1	2015	Ibrutinib (Imbruvica ) is a first-in-class, orally administered once-daily, that inhibits B-cell antigen receptor signaling downstream of Bruton"s tyrosine kinase (BTK).	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	164-167
26118882-2	2015	Ibrutinib has been approved in USA in February 2014 and in France in October 2014 for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL) or chronic lymphocytic leukaemia (CLL) and for the treatment of patients with CLL and a chromosome 17 deletion (del 17p) or TP53 mutation.	ibrutinib	0-9	tumor protein p53	Homo sapiens	288-292
25975443-13	2015	In addition, exciting options for relapsed MCL have emerged in the last few years, with the introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and the development of the lenalidomide-rituximab combination.	ibrutinib	151-160	Bruton tyrosine kinase	Homo sapiens	136-139
26942065-0	2016	Ibrutinib enhances IL-17 response by modulating the function of bone marrow derived dendritic cells.	ibrutinib	0-9	interleukin 17A	Homo sapiens	19-24
26942065-1	2016	Ibrutinib (PCI-32765) is an irreversible dual Btk/Itk inhibitor shown to be effective in treating several B cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	46-49
26942065-1	2016	Ibrutinib (PCI-32765) is an irreversible dual Btk/Itk inhibitor shown to be effective in treating several B cell malignancies.	ibrutinib	0-9	IL2 inducible T cell kinase	Homo sapiens	50-53
26942065-3	2016	Hence, we studied the effect of ibrutinib treatment on TLR-4 mediated activation of bone marrow derived dendritic cell culture (DCs).	ibrutinib	32-41	toll like receptor 4	Homo sapiens	55-60
26942065-4	2016	Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-alpha and nitric oxide (NO) and higher induction of IL-6, TGF-beta, IL-10 and IL-18.	ibrutinib	5-14	tumor necrosis factor	Homo sapiens	71-80
26942065-4	2016	Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-alpha and nitric oxide (NO) and higher induction of IL-6, TGF-beta, IL-10 and IL-18.	ibrutinib	5-14	interleukin 6	Homo sapiens	127-131
26942065-4	2016	Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-alpha and nitric oxide (NO) and higher induction of IL-6, TGF-beta, IL-10 and IL-18.	ibrutinib	5-14	transforming growth factor beta 1	Homo sapiens	133-141
26942065-4	2016	Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-alpha and nitric oxide (NO) and higher induction of IL-6, TGF-beta, IL-10 and IL-18.	ibrutinib	5-14	interleukin 10	Homo sapiens	143-148
26942065-4	2016	Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-alpha and nitric oxide (NO) and higher induction of IL-6, TGF-beta, IL-10 and IL-18.	ibrutinib	5-14	interleukin 18	Homo sapiens	153-158
26942065-5	2016	While ibrutinib dampened MHC-II and CD86 expression on DCs, CD80 expression was upregulated.	ibrutinib	6-15	CD86 molecule	Homo sapiens	36-40
26942065-6	2016	Further, ibrutinib-treated DCs promoted T cell proliferation and enhanced IL-17 production upon co-culture with nylon wool enriched T cells.	ibrutinib	9-18	interleukin 17A	Homo sapiens	74-79
26942065-7	2016	Taken together, our results indicate that ibrutinib modulates TLR-4 mediated DC activation to promote an IL-17 response.	ibrutinib	42-51	toll like receptor 4	Homo sapiens	62-67
26942065-7	2016	Taken together, our results indicate that ibrutinib modulates TLR-4 mediated DC activation to promote an IL-17 response.	ibrutinib	42-51	interleukin 17A	Homo sapiens	105-110
26022368-2	2015	In particular, ibrutinib, previously called PCI-32765, is a potent inhibitor of Bruton tyrosine kinase (Btk), recently approved for the treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).	ibrutinib	15-24	Bruton tyrosine kinase	Homo sapiens	104-107
26022368-2	2015	In particular, ibrutinib, previously called PCI-32765, is a potent inhibitor of Bruton tyrosine kinase (Btk), recently approved for the treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	80-102
26022368-2	2015	In particular, ibrutinib, previously called PCI-32765, is a potent inhibitor of Bruton tyrosine kinase (Btk), recently approved for the treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	104-107
24954503-2	2015	Especially the early clinical success of Ibrutinib, an irreversible inhibitor of Bruton"s tyrosine kinase (BTK), has received widespread attention.	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	81-105
25953974-1	2015	In this issue of Blood, Brown and colleagues show an impressive additional value when combining a tyrosine kinase inhibitor, that is, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, with classic chemoimmunotherapy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma	ibrutinib	177-186	Bruton tyrosine kinase	Homo sapiens	138-160
25953974-1	2015	In this issue of Blood, Brown and colleagues show an impressive additional value when combining a tyrosine kinase inhibitor, that is, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, with classic chemoimmunotherapy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma	ibrutinib	177-186	Bruton tyrosine kinase	Homo sapiens	162-165
26036311-0	2015	Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer.	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	0-24
26036311-0	2015	Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer.	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	26-29
25849561-0	2015	Direct and two-step bioorthogonal probes for Bruton"s tyrosine kinase based on ibrutinib: a comparative study.	ibrutinib	79-88	Bruton tyrosine kinase	Homo sapiens	45-69
25849561-1	2015	Ibrutinib is a covalent and irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and has been approved for the treatment of haematological malignancies, such as chronic lymphocytic leukaemia, mantle cell lymphoma and Waldenstrom"s macroglobulinemia.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	54-78
25849561-1	2015	Ibrutinib is a covalent and irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and has been approved for the treatment of haematological malignancies, such as chronic lymphocytic leukaemia, mantle cell lymphoma and Waldenstrom"s macroglobulinemia.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	80-83
25849561-3	2015	Fluorescent and biotinylated ibrutinib derivatives have appeared in the literature in recent years to monitor BTK in vitro and in situ.	ibrutinib	29-38	Bruton tyrosine kinase	Homo sapiens	110-113
24954503-2	2015	Especially the early clinical success of Ibrutinib, an irreversible inhibitor of Bruton"s tyrosine kinase (BTK), has received widespread attention.	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	107-110
24954503-3	2015	In this review we will focus on the fundamental and clinical aspects of BTK inhibitors in CLL, with emphasis on Ibrutinib as the best studied of this class of drugs.	ibrutinib	112-121	Bruton tyrosine kinase	Homo sapiens	72-75
25847947-6	2015	Pharmacological or dominant-negative JNK inhibition restricts DLBCL survival in vitro and in vivo and synergizes strongly with the Bruton"s tyrosine kinase inhibitor ibrutinib.	ibrutinib	166-175	mitogen-activated protein kinase 8	Homo sapiens	37-40
26688095-0	2015	Activity of Bruton"s tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells.	ibrutinib	47-56	Bruton tyrosine kinase	Homo sapiens	12-36
25669675-0	2015	Targeting Bruton"s tyrosine kinase with ibrutinib in B-cell malignancies.	ibrutinib	40-49	Bruton tyrosine kinase	Homo sapiens	10-34
25669675-2	2015	Ibrutinib is a potent irreversible inhibitor of Bruton"s tyrosine kinase (Btk), a key kinase important for signal transduction in the B-cell receptor (BCR) pathway.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	48-72
25669675-2	2015	Ibrutinib is a potent irreversible inhibitor of Bruton"s tyrosine kinase (Btk), a key kinase important for signal transduction in the B-cell receptor (BCR) pathway.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	74-77
25669675-3	2015	In preclinical studies, ibrutinib potently bound to Btk, inhibited BCR signaling, and decreased tumor cell proliferation and survival in many B-cell malignancy models.	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	52-55
25670208-4	2015	Ibrutinib is a potent, selective BTK inhibitor that has shown significant activity in specific subtypes of B-cell non-Hodgkin"s lymphomas (NHLs).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	33-36
25767114-7	2015	Ibrutinib, a Tec family kinase inhibitor, also completely abolished CLEC-2-mediated aggregation and Syk phosphorylation in human and murine platelets.	ibrutinib	0-9	tec protein tyrosine kinase	Homo sapiens	13-16
25767114-7	2015	Ibrutinib, a Tec family kinase inhibitor, also completely abolished CLEC-2-mediated aggregation and Syk phosphorylation in human and murine platelets.	ibrutinib	0-9	C-type lectin domain family 1 member B	Homo sapiens	68-74
25767114-7	2015	Ibrutinib, a Tec family kinase inhibitor, also completely abolished CLEC-2-mediated aggregation and Syk phosphorylation in human and murine platelets.	ibrutinib	0-9	spleen associated tyrosine kinase	Homo sapiens	100-103
25486872-0	2015	miR-155 expression is associated with chemoimmunotherapy outcome and is modulated by Bruton"s tyrosine kinase inhibition with Ibrutinib.	ibrutinib	126-135	microRNA 155	Homo sapiens	0-7
25908509-14	2015	Patients with a del(17p) or TP53 mutation can be treated with ibrutinib or a combination of idelalisib and rituximab.	ibrutinib	62-71	tumor protein p53	Homo sapiens	28-32
25802231-1	2015	Ibrutinib (Imbruvica ) is a first-in-class, potent, orally administered, covalent inhibitor of Bruton"s tyrosine kinase (BTK) that inhibits B-cell antigen receptor signalling downstream of BTK.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	95-119
25802231-1	2015	Ibrutinib (Imbruvica ) is a first-in-class, potent, orally administered, covalent inhibitor of Bruton"s tyrosine kinase (BTK) that inhibits B-cell antigen receptor signalling downstream of BTK.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	121-124
25802231-1	2015	Ibrutinib (Imbruvica ) is a first-in-class, potent, orally administered, covalent inhibitor of Bruton"s tyrosine kinase (BTK) that inhibits B-cell antigen receptor signalling downstream of BTK.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	189-192
25802231-1	2015	Ibrutinib (Imbruvica ) is a first-in-class, potent, orally administered, covalent inhibitor of Bruton"s tyrosine kinase (BTK) that inhibits B-cell antigen receptor signalling downstream of BTK.	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	95-119
25802231-1	2015	Ibrutinib (Imbruvica ) is a first-in-class, potent, orally administered, covalent inhibitor of Bruton"s tyrosine kinase (BTK) that inhibits B-cell antigen receptor signalling downstream of BTK.	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	121-124
25802231-1	2015	Ibrutinib (Imbruvica ) is a first-in-class, potent, orally administered, covalent inhibitor of Bruton"s tyrosine kinase (BTK) that inhibits B-cell antigen receptor signalling downstream of BTK.	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	189-192
25802231-2	2015	Oral ibrutinib is indicated for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL) or chronic lymphocytic leukaemia (CLL) and for the treatment of patients with CLL and a chromosome 17 deletion (del 17p) or TP53 mutation.	ibrutinib	5-14	tumor protein p53	Homo sapiens	234-238
25802231-7	2015	Given its efficacy and tolerability, once-daily, oral ibrutinib is an emerging treatment option for patients with relapsed/refractory MCL or CLL and CLL patients with del 17p or TP53 mutation.	ibrutinib	54-63	tumor protein p53	Homo sapiens	178-182
26688095-0	2015	Activity of Bruton"s tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells.	ibrutinib	47-56	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	74-79
26688095-1	2015	BACKGROUND: Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton"s tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in vitro.	ibrutinib	236-245	Bruton tyrosine kinase	Homo sapiens	87-111
26688095-1	2015	BACKGROUND: Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton"s tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in vitro.	ibrutinib	236-245	Bruton tyrosine kinase	Homo sapiens	113-116
26688095-2	2015	We aimed to develop the biological understanding of the BTK pathway in acute myeloid leukaemia to identify clinically relevant diagnostic information that might define a subset of patients that should respond to ibrutinib treatment.	ibrutinib	212-221	Bruton tyrosine kinase	Homo sapiens	56-59
26688095-5	2015	Furthermore, we investigated the effects of ibrutinib on CD117-induced BTK activation, downstream signalling, adhesion to primary bone-marrow mesenchymal stromal cells, and proliferation of primary acute myeloid leukaemia blast cells.	ibrutinib	44-53	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	57-62
26688095-8	2015	Ibrutinib significantly inhibited CD117-mediated proliferation of primary acute myeloid leukaemia blast cells (p=0 028).	ibrutinib	0-9	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	34-39
26688095-10	2015	Furthermore, ibrutinib inhibited CD117-induced activity of BTK and downstream kinases at a concentration of 100 nM or more.	ibrutinib	13-22	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	33-38
26688095-10	2015	Furthermore, ibrutinib inhibited CD117-induced activity of BTK and downstream kinases at a concentration of 100 nM or more.	ibrutinib	13-22	Bruton tyrosine kinase	Homo sapiens	59-62
26688095-11	2015	CD117-mediated adhesion of CD117-expressing blast cells to bone-marrow stromal cells was significantly inhibited by Ibrutinib at 500 nM (p=0 028) INTERPRETATION: As first-in-man clinical trials of ibrutinib in patients with acute myeloid leukaemia commence, the data suggest not all patients will respond.	ibrutinib	116-125	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	0-5
26688095-11	2015	CD117-mediated adhesion of CD117-expressing blast cells to bone-marrow stromal cells was significantly inhibited by Ibrutinib at 500 nM (p=0 028) INTERPRETATION: As first-in-man clinical trials of ibrutinib in patients with acute myeloid leukaemia commence, the data suggest not all patients will respond.	ibrutinib	116-125	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	27-32
26688095-11	2015	CD117-mediated adhesion of CD117-expressing blast cells to bone-marrow stromal cells was significantly inhibited by Ibrutinib at 500 nM (p=0 028) INTERPRETATION: As first-in-man clinical trials of ibrutinib in patients with acute myeloid leukaemia commence, the data suggest not all patients will respond.	ibrutinib	197-206	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	0-5
26688095-11	2015	CD117-mediated adhesion of CD117-expressing blast cells to bone-marrow stromal cells was significantly inhibited by Ibrutinib at 500 nM (p=0 028) INTERPRETATION: As first-in-man clinical trials of ibrutinib in patients with acute myeloid leukaemia commence, the data suggest not all patients will respond.	ibrutinib	197-206	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	27-32
26688095-12	2015	Our findings show that BTK has specific pro-tumoural biological actions downstream of surface CD117 activation, which are inhibited by ibrutinib.	ibrutinib	135-144	Bruton tyrosine kinase	Homo sapiens	23-26
26688095-12	2015	Our findings show that BTK has specific pro-tumoural biological actions downstream of surface CD117 activation, which are inhibited by ibrutinib.	ibrutinib	135-144	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	94-99
26688095-13	2015	Accordingly, we propose that patients with acute myeloid leukaemia whose blast cells express CD117 should be considered for forthcoming clinical trials of ibrutinib.	ibrutinib	155-164	KIT proto-oncogene, receptor tyrosine kinase	Homo sapiens	93-98
25138588-1	2015	The BTK (Bruton"s tyrosine kinase) inhibitor ibrutinib is associated with an increased risk of bleeding.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-7
25883227-1	2015	In this issue of Blood, Byrd et al provide an important update on the prolonged efficacy and the limited and reducing toxicity of the single-agent Bruton tyrosine kinase inhibitor ibrutinib in chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma patients who are followed for a median time of 3 years from start of treatment.	ibrutinib	180-189	Bruton tyrosine kinase	Homo sapiens	147-169
25853747-2	2015	MYD88(L265P) triggers tumor-cell growth through Bruton"s tyrosine kinase, a target of ibrutinib.	ibrutinib	86-95	MYD88 innate immune signal transduction adaptor	Homo sapiens	0-5
25853747-2	2015	MYD88(L265P) triggers tumor-cell growth through Bruton"s tyrosine kinase, a target of ibrutinib.	ibrutinib	86-95	Bruton tyrosine kinase	Homo sapiens	48-72
25853747-3	2015	CXCR4(WHIM) mutations confer in vitro resistance to ibrutinib.	ibrutinib	52-61	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
25826029-16	2015	Ibrutinib acts by inhibiting the Bruton"s tyrosine kinase (BTK) while idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	33-57
25826029-16	2015	Ibrutinib acts by inhibiting the Bruton"s tyrosine kinase (BTK) while idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	59-62
25138588-1	2015	The BTK (Bruton"s tyrosine kinase) inhibitor ibrutinib is associated with an increased risk of bleeding.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	9-33
25189416-0	2015	Functional characterization of BTK(C481S) mutation that confers ibrutinib resistance: exploration of alternative kinase inhibitors.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	31-34
25189416-1	2015	The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has produced remarkable clinical response in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	4-26
25189416-1	2015	The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has produced remarkable clinical response in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	28-31
25189416-2	2015	We previously reported the identification of BTK(C481S) mutation in a CLL patient who progressed following 21-month ibrutinib therapy.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	45-48
25189416-3	2015	Initial characterization at structural and biochemical levels revealed that the mutation disrupts the covalent binding of ibrutinib to BTK, reduces its binding affinity and diminishes its ability to inhibit the BTK enzymatic activity.	ibrutinib	122-131	Bruton tyrosine kinase	Homo sapiens	135-138
25189416-3	2015	Initial characterization at structural and biochemical levels revealed that the mutation disrupts the covalent binding of ibrutinib to BTK, reduces its binding affinity and diminishes its ability to inhibit the BTK enzymatic activity.	ibrutinib	122-131	Bruton tyrosine kinase	Homo sapiens	211-214
25662332-0	2015	Ibrutinib enhances the antitumor immune response induced by intratumoral injection of a TLR9 ligand in mouse lymphoma.	ibrutinib	0-9	toll-like receptor 9	Mus musculus	88-92
26182309-1	2015	IMPORTANCE: The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in patients with chronic lymphocytic leukemia (CLL).	ibrutinib	55-64	Bruton tyrosine kinase	Homo sapiens	16-38
26182309-1	2015	IMPORTANCE: The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in patients with chronic lymphocytic leukemia (CLL).	ibrutinib	55-64	Bruton tyrosine kinase	Homo sapiens	40-43
25805587-6	2015	Pharmacological inhibition with ibrutinib of Bruton"s tyrosine kinase, a kinase that is required for BCR signaling to engage NF-kappaB, is selectively toxic for ABC DLBCL tumors; a finding that has now been translated to the clinic.	ibrutinib	32-41	Bruton tyrosine kinase	Homo sapiens	45-69
25730880-0	2015	Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK.	ibrutinib	69-78	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	101-104
25730880-0	2015	Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK.	ibrutinib	69-78	IL2 inducible T cell kinase	Mus musculus	109-112
25730880-2	2015	Ibrutinib, an approved therapy for B-cell malignancies, is a covalent inhibitor of BTK, a member of the B-cell receptor (BCR) signaling pathway, which is critical to the survival of malignant B cells.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	83-86
25730880-6	2015	The enhanced therapeutic activity of PD-L1 blockade by ibrutinib was accompanied by enhanced antitumor T-cell immune responses.	ibrutinib	55-64	CD274 antigen	Mus musculus	37-42
25730880-7	2015	These preclinical results suggest that the combination of PD1/PD1-L blockade and ibrutinib should be tested in the clinic for the therapy not only of lymphoma but also in other hematologic malignancies and solid tumors that do not even express BTK.	ibrutinib	81-90	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	244-247
25632006-1	2015	BCR signaling pathway inhibitors such as ibrutinib, idelalisib, and fostamatinib (respective inhibitors of Bruton"s tyrosine kinase, PI3Kdelta, and spleen tyrosine kinase) represent a significant therapeutic advance in B cell malignancies, including chronic lymphocytic leukemia (CLL).	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	107-131
25080849-3	2015	This has recently been underscored by clinical trials demonstrating that small molecules (fosfamatinib, ibrutinib, idelalisib) inhibiting BCR-associated kinases (SYK, BTK, PI3K) have an encouraging clinical effect.	ibrutinib	104-113	Bruton tyrosine kinase	Homo sapiens	167-170
25080849-3	2015	This has recently been underscored by clinical trials demonstrating that small molecules (fosfamatinib, ibrutinib, idelalisib) inhibiting BCR-associated kinases (SYK, BTK, PI3K) have an encouraging clinical effect.	ibrutinib	104-113	spleen associated tyrosine kinase	Homo sapiens	162-165
25632006-1	2015	BCR signaling pathway inhibitors such as ibrutinib, idelalisib, and fostamatinib (respective inhibitors of Bruton"s tyrosine kinase, PI3Kdelta, and spleen tyrosine kinase) represent a significant therapeutic advance in B cell malignancies, including chronic lymphocytic leukemia (CLL).	ibrutinib	41-50	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta	Homo sapiens	133-142
25993154-5	2015	The BCR signaling pathway inhibitors (ibrutinib targeting Bruton"s tyrosine kinase [BTK] and idelalisib targeting phosphatidyl-inositol 3-kinase delta [PI3K-delta], respectively) are currently approved for the treatment of relapsed/refractory CLL and all patients with 17p- (ibrutinib), and in combination with rituximab for relapsed/refractory patients (idelalisib).	ibrutinib	38-47	Bruton tyrosine kinase	Homo sapiens	58-82
25589346-1	2015	Ibrutinib (Imbruvica), a small-drug inhibitor of Bruton tyrosine kinase (BTK), is currently undergoing clinical testing in patients with multiple myeloma, yet important questions on the role of BTK in myeloma biology and treatment are outstanding.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	49-71
25589346-1	2015	Ibrutinib (Imbruvica), a small-drug inhibitor of Bruton tyrosine kinase (BTK), is currently undergoing clinical testing in patients with multiple myeloma, yet important questions on the role of BTK in myeloma biology and treatment are outstanding.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	73-76
25589346-1	2015	Ibrutinib (Imbruvica), a small-drug inhibitor of Bruton tyrosine kinase (BTK), is currently undergoing clinical testing in patients with multiple myeloma, yet important questions on the role of BTK in myeloma biology and treatment are outstanding.	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	49-71
25589346-1	2015	Ibrutinib (Imbruvica), a small-drug inhibitor of Bruton tyrosine kinase (BTK), is currently undergoing clinical testing in patients with multiple myeloma, yet important questions on the role of BTK in myeloma biology and treatment are outstanding.	ibrutinib	11-20	Bruton tyrosine kinase	Homo sapiens	73-76
25555420-0	2015	Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial.	ibrutinib	0-9	tumor protein p53	Homo sapiens	97-101
25555420-2	2015	We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53 aberrations.	ibrutinib	43-52	tumor protein p53	Homo sapiens	113-117
25555420-17	2015	INTERPRETATION: The activity and safety profile of single-agent ibrutinib in CLL with TP53 aberrations is encouraging and supports its consideration as a novel treatment option for patients with this high-risk disease in both first-line and second-line settings.	ibrutinib	64-73	tumor protein p53	Homo sapiens	86-90
25565020-0	2015	Ibrutinib inhibits BTK-driven NF-kappaB p65 activity to overcome bortezomib-resistance in multiple myeloma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	19-22
25655613-9	2015	Therapy for relapsed disease is dependent on prior treatment, age, comorbidities, and toxicities but includes targeted therapies such as the Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib, the immunomodulatory agent lenalidomide, the proteasome inhibitor bortezomib, combination chemoimmunotherapy, ASCT, and allogeneic stem cell transplant in selected cases.	ibrutinib	182-191	Bruton tyrosine kinase	Homo sapiens	141-165
25565020-0	2015	Ibrutinib inhibits BTK-driven NF-kappaB p65 activity to overcome bortezomib-resistance in multiple myeloma.	ibrutinib	0-9	RELA proto-oncogene, NF-kB subunit	Homo sapiens	40-43
26165513-5	2015	The oral BTK inhibitor ibrutinib is already US FDA approved in four different indications based on marked treatment benefit in indolent B cell lymphoma/leukemia.	ibrutinib	23-32	Bruton tyrosine kinase	Homo sapiens	9-12
25975016-2	2015	Ibrutinib (Imbruvica) is metabolized in the liver mainly by the isoenzyme CYP3A4 and to a minor extent by CYP2D6.	ibrutinib	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	74-80
25975016-2	2015	Ibrutinib (Imbruvica) is metabolized in the liver mainly by the isoenzyme CYP3A4 and to a minor extent by CYP2D6.	ibrutinib	0-9	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	106-112
25975016-2	2015	Ibrutinib (Imbruvica) is metabolized in the liver mainly by the isoenzyme CYP3A4 and to a minor extent by CYP2D6.	ibrutinib	11-20	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	74-80
25975016-2	2015	Ibrutinib (Imbruvica) is metabolized in the liver mainly by the isoenzyme CYP3A4 and to a minor extent by CYP2D6.	ibrutinib	11-20	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	106-112
26165513-8	2015	EXPERT OPINION: Ibrutinib is a well-tolerated once-daily oral BTK inhibitor with impressive activity in treating indolent B cell lymphoproliferative disorders.	ibrutinib	16-25	Bruton tyrosine kinase	Homo sapiens	62-65
26637744-5	2015	New B-cell receptor inhibitors, such as ibrutinib and idelalisib, may have a role in the management of B-PLL, especially for the patients harboring abnormalities of TP53.	ibrutinib	40-49	tumor protein p53	Homo sapiens	165-169
25344523-0	2015	Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy.	ibrutinib	0-9	keratin 20	Homo sapiens	81-85
25344523-1	2015	The novel Bruton tyrosine kinase inhibitor ibrutinib and phosphatidyl-4-5-biphosphate 3-kinase-delta inhibitor idelalisib are promising drugs for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies.	ibrutinib	43-52	keratin 20	Homo sapiens	266-270
25344523-5	2015	In contrast, ibrutinib strongly inhibited all cell-mediated mechanisms induced by anti-CD20 antibodies rituximab, ofatumumab or obinutuzumab, either in purified systems or whole blood assays.	ibrutinib	13-22	keratin 20	Homo sapiens	87-91
24901734-0	2015	The HELIOS trial protocol: a phase III study of ibrutinib in combination with bendamustine and rituximab in relapsed/refractory chronic lymphocytic leukemia.	ibrutinib	48-57	IKAROS family zinc finger 2	Homo sapiens	4-10
25344523-7	2015	Analysis of anti-CD20 mediated activation of natural killer cells isolated from patients on continued oral ibrutinib treatment suggested that repeated drug dosing inhibits these cells in vivo.	ibrutinib	107-116	keratin 20	Homo sapiens	17-21
26637745-6	2015	Ibrutinib and idelalisib are currently approved for the treatment of relapsed or refractory CLL or frontline treatment of 17p-/TP53mut CLL regardless of fitness.	ibrutinib	0-9	tumor protein p53	Homo sapiens	127-131
26062943-6	2015	Fortunately, significant progress in the understanding of CLL biology has enabled the development of new molecular drugs targeting the B-cell receptor signaling pathway, such as ibrutinib and idelalisib, which have shown impressive results in patients with relapsed/refractory disease or with TP53 mutation/deletion.	ibrutinib	178-187	tumor protein p53	Homo sapiens	293-297
24912431-0	2015	The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom"s Macroglobulinemia.	ibrutinib	94-103	C-X-C motif chemokine receptor 4	Homo sapiens	14-19
24912431-0	2015	The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom"s Macroglobulinemia.	ibrutinib	94-103	AKT serine/threonine kinase 1	Homo sapiens	54-57
24912431-0	2015	The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom"s Macroglobulinemia.	ibrutinib	94-103	mitogen-activated protein kinase 1	Homo sapiens	62-65
24912431-1	2015	CXCR4(WHIM) somatic mutations are common Waldenstrom"s Macroglobulinemia (WM), and are associated with clinical resistance to ibrutinib.	ibrutinib	126-135	C-X-C motif chemokine receptor 4	Homo sapiens	0-5
26237681-5	2015	Since Bruton"s Tyrosine Kinase (BTK) plays a significant role for the survival of ABC lymphoma, this study also combined the BTK inhibitor ibrutinib with temsirolimus, which resulted in additive cell growth reduction (ibrutinib 50%, temsirolimus 44%, combination 25%) in ABC lymphoma.	ibrutinib	139-148	Bruton tyrosine kinase	Homo sapiens	125-128
24912431-5	2015	SDF-1a-treated CXCR4(S338X) WM cells showed sustained AKT and ERK activation and decreased apoptotic changes versus CXCR4(WT) cells following ibrutinib treatment, findings which were also reversed by AMD3100.	ibrutinib	142-151	C-X-C motif chemokine receptor 4	Homo sapiens	15-20
24912431-6	2015	AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance.	ibrutinib	32-41	AKT serine/threonine kinase 1	Homo sapiens	0-3
24912431-6	2015	AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance.	ibrutinib	32-41	mitogen-activated protein kinase 1	Homo sapiens	7-10
24912431-6	2015	AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance.	ibrutinib	32-41	C-X-C motif chemokine receptor 4	Homo sapiens	88-93
25258342-6	2014	Furthermore, IPI-145 overcomes the ibrutinib resistance resulting from treatment-induced BTK C481S mutation.	ibrutinib	35-44	Bruton tyrosine kinase	Homo sapiens	89-92
24912431-6	2015	AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance.	ibrutinib	154-163	AKT serine/threonine kinase 1	Homo sapiens	0-3
24912431-6	2015	AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance.	ibrutinib	154-163	mitogen-activated protein kinase 1	Homo sapiens	7-10
24912431-6	2015	AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance.	ibrutinib	154-163	C-X-C motif chemokine receptor 4	Homo sapiens	88-93
25305202-0	2014	Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions.	ibrutinib	0-9	von Willebrand factor	Homo sapiens	41-62
25305202-3	2014	We demonstrate that ibrutinib selectively inhibits platelet signaling and functions downstream of the collagen receptor glycoprotein VI and strongly affects firm platelet adhesion on von Willebrand factor (VWF) under arterial flow.	ibrutinib	20-29	von Willebrand factor	Homo sapiens	183-204
25305202-3	2014	We demonstrate that ibrutinib selectively inhibits platelet signaling and functions downstream of the collagen receptor glycoprotein VI and strongly affects firm platelet adhesion on von Willebrand factor (VWF) under arterial flow.	ibrutinib	20-29	von Willebrand factor	Homo sapiens	206-209
25696845-5	2014	Ibrutinib, a covalent inhibitor of BTK approved by the Food and Drug Administration as a second-line treatment for CLL, and idelalisib, a selective inhibitor of PI3Kdelta, achieve excellent clinical responses in both diseases irrespective of classic markers indicating high-risk disease.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	35-38
25164592-14	2014	CONCLUSIONS AND IMPLICATIONS: Our results indicated that ibrutinib significantly increased the efficacy of the chemotherapeutic agents which were MRP1 substrates, in MRP1-overexpressing cells, in vitro, in vivo and ex vivo.	ibrutinib	57-66	ATP binding cassette subfamily B member 1	Homo sapiens	166-170
25164592-15	2014	These findings will lead to further studies on the effects of a combination of ibrutinib with chemotherapeutic agents in cancer patients overexpressing MRP1.	ibrutinib	79-88	ATP binding cassette subfamily B member 1	Homo sapiens	152-156
25164592-0	2014	In vitro, in vivo and ex vivo characterization of ibrutinib: a potent inhibitor of the efflux function of the transporter MRP1.	ibrutinib	50-59	ATP binding cassette subfamily B member 1	Homo sapiens	122-126
25164592-3	2014	Here we investigated the reversal effect of ibrutinib on MRP1-mediated MDR.	ibrutinib	44-53	ATP binding cassette subfamily B member 1	Homo sapiens	57-61
25164592-9	2014	KEY RESULTS: Ibrutinib significantly enhanced the cytotoxicity of MRP1 substrates in HEK293/MRP1 and HL60/Adr cells overexpressing MRP1.	ibrutinib	13-22	ATP binding cassette subfamily B member 1	Homo sapiens	66-70
25164592-9	2014	KEY RESULTS: Ibrutinib significantly enhanced the cytotoxicity of MRP1 substrates in HEK293/MRP1 and HL60/Adr cells overexpressing MRP1.	ibrutinib	13-22	ATP binding cassette subfamily B member 1	Homo sapiens	92-96
25081321-0	2014	Ibrutinib (ImbruvicaTM) potently inhibits ErbB receptor phosphorylation and cell viability of ErbB2-positive breast cancer cells.	ibrutinib	0-9	epidermal growth factor receptor	Homo sapiens	42-46
25164592-9	2014	KEY RESULTS: Ibrutinib significantly enhanced the cytotoxicity of MRP1 substrates in HEK293/MRP1 and HL60/Adr cells overexpressing MRP1.	ibrutinib	13-22	ATP binding cassette subfamily B member 1	Homo sapiens	92-96
25164592-10	2014	Furthermore, ibrutinib increased the accumulation of substrates in these MRP1-overexpressing cells by inhibiting the drug efflux function of MRP1.	ibrutinib	13-22	ATP binding cassette subfamily B member 1	Homo sapiens	73-77
25164592-10	2014	Furthermore, ibrutinib increased the accumulation of substrates in these MRP1-overexpressing cells by inhibiting the drug efflux function of MRP1.	ibrutinib	13-22	ATP binding cassette subfamily B member 1	Homo sapiens	141-145
25164592-11	2014	However, mRNA and protein expression of MRP1 remained unaltered after treatment with ibrutinib in MRP1-overexpressing cells.	ibrutinib	85-94	ATP binding cassette subfamily B member 1	Homo sapiens	98-102
25164592-12	2014	In vivo, ibrutinib enhanced the efficacy of vincristine to inhibit the growth of HEK293/MRP1 tumour xenografts in nude mice.	ibrutinib	9-18	ATP-binding cassette, sub-family C (CFTR/MRP), member 1	Mus musculus	88-92
25164592-14	2014	CONCLUSIONS AND IMPLICATIONS: Our results indicated that ibrutinib significantly increased the efficacy of the chemotherapeutic agents which were MRP1 substrates, in MRP1-overexpressing cells, in vitro, in vivo and ex vivo.	ibrutinib	57-66	ATP binding cassette subfamily B member 1	Homo sapiens	146-150
25081321-0	2014	Ibrutinib (ImbruvicaTM) potently inhibits ErbB receptor phosphorylation and cell viability of ErbB2-positive breast cancer cells.	ibrutinib	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	94-99
25392275-7	2014	In 2014, several new compounds were approved for patients with ultrahigh risk genetic factors (17p-, TP53mut) and for relapsed/refractory CLL: both idelalisib and ibrutinib are orally bioavailable kinase inhibitors that block key regulators of central pathways.	ibrutinib	163-172	tumor protein p53	Homo sapiens	101-105
25081321-1	2014	Ibrutinib (formerly PCI-32765) is a specific, irreversible, and potent inhibitor of Burton"s tyrosine kinase (BTK) developed for the treatment of several forms of blood cancer.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	110-113
25081321-5	2014	We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines.	ibrutinib	20-29	epidermal growth factor receptor	Homo sapiens	103-108
25081321-5	2014	We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines.	ibrutinib	20-29	erb-b2 receptor tyrosine kinase 2	Homo sapiens	110-115
25081321-5	2014	We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines.	ibrutinib	20-29	erb-b2 receptor tyrosine kinase 3	Homo sapiens	120-125
25081321-5	2014	We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines.	ibrutinib	20-29	AKT serine/threonine kinase 1	Homo sapiens	147-150
25081321-5	2014	We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines.	ibrutinib	20-29	erb-b2 receptor tyrosine kinase 2	Homo sapiens	173-178
25081321-5	2014	We demonstrate that Ibrutinib efficiently reduces the phosphorylation of the receptor tyrosine kinases ErbB1, ErbB2 and ErbB3, thereby suppressing AKT and MAPK signaling in ErbB2-positive (ErbB2+) breast cancer cell lines.	ibrutinib	20-29	erb-b2 receptor tyrosine kinase 2	Homo sapiens	173-178
25081321-6	2014	Treatment with Ibrutinib significantly reduced the viability of ErbB2+ cell lines with IC50 values at nanomolar concentrations, suggesting therapeutic potential of Ibrutinib in breast cancer.	ibrutinib	15-24	erb-b2 receptor tyrosine kinase 2	Homo sapiens	64-69
25081321-6	2014	Treatment with Ibrutinib significantly reduced the viability of ErbB2+ cell lines with IC50 values at nanomolar concentrations, suggesting therapeutic potential of Ibrutinib in breast cancer.	ibrutinib	164-173	erb-b2 receptor tyrosine kinase 2	Homo sapiens	64-69
25081321-7	2014	Combined treatment with Ibrutinib and the dual PI3K/mTOR inhibitor BEZ235 synergistically reduces cell viability of ErbB2+ breast cancer cells.	ibrutinib	24-33	erb-b2 receptor tyrosine kinase 2	Homo sapiens	116-121
25081321-9	2014	Therefore, the combination of Ibrutinib and canonical PI3K pathway inhibitors could be a new and effective approach in the treatment of breast cancer with activated ErbB receptors.	ibrutinib	30-39	epidermal growth factor receptor	Homo sapiens	165-169
25081321-10	2014	Ibrutinib could thus become a valuable component of targeted therapy in aggressive ErbB2+ breast cancer.	ibrutinib	0-9	erb-b2 receptor tyrosine kinase 2	Homo sapiens	83-88
25271622-3	2014	Ibrutinib is an FDA-approved irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissions in B cell malignancies with minimal toxicity.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	55-79
24625454-10	2014	CONCLUSIONS: The future for new treatment options in DLBCL is promising with current clinical trials testing novel targeted agents such as bortezomib, lenalidomide, and ibrutinib as the "X" in R(X)CHOP.	ibrutinib	169-178	DNA damage inducible transcript 3	Homo sapiens	197-201
25361916-1	2014	Ibrutinib (PCI-32765)--a potent, covalent inhibitor of Bruton tyrosine kinase (BTK), an important kinase in the B-cell receptor signaling pathway--was recently approved by the FDA for the treatment of relapsed or refractory mantle cell lymphoma (MCL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	55-77
25361916-1	2014	Ibrutinib (PCI-32765)--a potent, covalent inhibitor of Bruton tyrosine kinase (BTK), an important kinase in the B-cell receptor signaling pathway--was recently approved by the FDA for the treatment of relapsed or refractory mantle cell lymphoma (MCL).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	79-82
25271622-3	2014	Ibrutinib is an FDA-approved irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissions in B cell malignancies with minimal toxicity.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	81-84
25271622-3	2014	Ibrutinib is an FDA-approved irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissions in B cell malignancies with minimal toxicity.	ibrutinib	0-9	IL2 inducible T cell kinase	Mus musculus	90-118
25271622-3	2014	Ibrutinib is an FDA-approved irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissions in B cell malignancies with minimal toxicity.	ibrutinib	0-9	IL2 inducible T cell kinase	Mus musculus	120-123
24957109-1	2014	Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	19-41
25294819-0	2014	Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML.	ibrutinib	0-9	C-X-C motif chemokine ligand 12	Homo sapiens	19-23
25294819-0	2014	Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML.	ibrutinib	0-9	C-X-C motif chemokine receptor 4	Homo sapiens	24-29
25294819-1	2014	Pharmacological targeting of BTK using ibrutinib has recently shown encouraging clinical activity in a range of lymphoid malignancies.	ibrutinib	39-48	Bruton tyrosine kinase	Homo sapiens	29-32
25294819-3	2014	Here we report that in human AML ibrutinib, in addition, functions to inhibit SDF1/CXCR4-mediated AML migration at concentrations achievable in vivo.	ibrutinib	33-42	C-X-C motif chemokine ligand 12	Homo sapiens	78-82
25294819-3	2014	Here we report that in human AML ibrutinib, in addition, functions to inhibit SDF1/CXCR4-mediated AML migration at concentrations achievable in vivo.	ibrutinib	33-42	C-X-C motif chemokine receptor 4	Homo sapiens	83-88
25294819-6	2014	Furthermore, we show that ibrutinib can inhibit SDF1-induced AKT and MAPK activation.	ibrutinib	26-35	C-X-C motif chemokine ligand 12	Homo sapiens	48-52
25294819-6	2014	Furthermore, we show that ibrutinib can inhibit SDF1-induced AKT and MAPK activation.	ibrutinib	26-35	AKT serine/threonine kinase 1	Homo sapiens	61-64
25294819-7	2014	These results reported here provide a molecular mechanistic rationale for clinically evaluating BTK inhibition in AML patients and suggests that in some AML patients the blasts count may initially rise in response to ibrutinib therapy, analgous to similar clinical observations in CLL.	ibrutinib	217-226	Bruton tyrosine kinase	Homo sapiens	96-99
25158606-5	2014	Ibrutinib is an orally active, Bruton"s tyrosine kinase inhibitor.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	31-55
25201956-1	2014	The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib is a new targeted therapy for patients with chronic lymphocytic leukemia (CLL).	ibrutinib	44-53	inhibitor of Bruton tyrosine kinase	Homo sapiens	4-36
25201956-1	2014	The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib is a new targeted therapy for patients with chronic lymphocytic leukemia (CLL).	ibrutinib	44-53	inhibitor of Bruton tyrosine kinase	Homo sapiens	38-42
25201956-6	2014	Our kinetic models predict that BTKi-resistant mutants exist before initiation of ibrutinib therapy, although they only comprise a minority of the overall tumor burden.	ibrutinib	82-91	inhibitor of Bruton tyrosine kinase	Homo sapiens	32-36
25214559-0	2014	Selective antitumor activity of ibrutinib in EGFR-mutant non-small cell lung cancer cells.	ibrutinib	32-41	epidermal growth factor receptor	Mus musculus	45-49
25214559-1	2014	Ibrutinib, which irreversibly inhibits Bruton tyrosine kinase, was evaluated for antitumor activity in a panel of non-small cell lung cancer (NSCLC) cell lines and found to selectively inhibit growth of NSCLC cells carrying mutations in the epidermal growth factor receptor (EGFR) gene, including T790M mutant and erlotinib-resistant H1975 cells.	ibrutinib	0-9	epidermal growth factor receptor	Homo sapiens	241-273
25214559-1	2014	Ibrutinib, which irreversibly inhibits Bruton tyrosine kinase, was evaluated for antitumor activity in a panel of non-small cell lung cancer (NSCLC) cell lines and found to selectively inhibit growth of NSCLC cells carrying mutations in the epidermal growth factor receptor (EGFR) gene, including T790M mutant and erlotinib-resistant H1975 cells.	ibrutinib	0-9	epidermal growth factor receptor	Homo sapiens	275-279
25214559-2	2014	Ibrutinib induced dose-dependent inhibition of phosphor-EGFR at both Y1068 and Y1173 sites, suggesting ibrutinib functions as an EGFR inhibitor.	ibrutinib	0-9	epidermal growth factor receptor	Mus musculus	56-60
25214559-2	2014	Ibrutinib induced dose-dependent inhibition of phosphor-EGFR at both Y1068 and Y1173 sites, suggesting ibrutinib functions as an EGFR inhibitor.	ibrutinib	0-9	epidermal growth factor receptor	Mus musculus	129-133
25214559-2	2014	Ibrutinib induced dose-dependent inhibition of phosphor-EGFR at both Y1068 and Y1173 sites, suggesting ibrutinib functions as an EGFR inhibitor.	ibrutinib	103-112	epidermal growth factor receptor	Mus musculus	56-60
25214559-2	2014	Ibrutinib induced dose-dependent inhibition of phosphor-EGFR at both Y1068 and Y1173 sites, suggesting ibrutinib functions as an EGFR inhibitor.	ibrutinib	103-112	epidermal growth factor receptor	Mus musculus	129-133
25214559-7	2014	Our results indicate that ibrutinib could be a candidate drug for treatment of EGFR-mutant NSCLC, including erlotinib-resistant tumors.	ibrutinib	26-35	epidermal growth factor receptor	Mus musculus	79-83
25222877-4	2014	Most importantly, 19 was able to induce a 63% reduction in Rec-1 cell proliferation, which was significantly greater than the 31% and 3% blockade of proliferation observed after cell treatment with R406, a Syk inhibitor, and ibrutinib, a Btk inhibitor, respectively.	ibrutinib	225-234	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	238-241
24957109-1	2014	Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	43-46
24957109-7	2014	Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities.	ibrutinib	76-85	Bruton tyrosine kinase	Homo sapiens	21-24
24957109-7	2014	Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities.	ibrutinib	76-85	Bruton tyrosine kinase	Homo sapiens	169-172
24957109-7	2014	Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities.	ibrutinib	146-155	Bruton tyrosine kinase	Homo sapiens	21-24
25082755-7	2014	SIGNIFICANCE: We have discovered the first relapse-specific BTK mutation in patients with MCL with acquired resistance, but not primary resistance, to ibrutinib, and demonstrated a rationale for targeting the proliferative resistant MCL cells by inhibiting CDK4 and the cell cycle in combination with ibrutinib in the presence of BTK(WT) or a PI3K inhibitor independent of BTK mutation.	ibrutinib	301-310	cyclin dependent kinase 4	Homo sapiens	257-261
25082755-1	2014	UNLABELLED: Despite the unprecedented clinical activity of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib in mantle cell lymphoma (MCL), acquired resistance is common.	ibrutinib	102-111	Bruton tyrosine kinase	Homo sapiens	63-85
24957109-7	2014	Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities.	ibrutinib	146-155	Bruton tyrosine kinase	Homo sapiens	169-172
25082755-1	2014	UNLABELLED: Despite the unprecedented clinical activity of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib in mantle cell lymphoma (MCL), acquired resistance is common.	ibrutinib	102-111	Bruton tyrosine kinase	Homo sapiens	87-90
25082755-2	2014	By longitudinal integrative whole-exome and whole-transcriptome sequencing and targeted sequencing, we identified the first relapse-specific C481S mutation at the ibrutinib binding site of BTK in MCL cells at progression following a durable response.	ibrutinib	163-172	Bruton tyrosine kinase	Homo sapiens	189-192
25082755-5	2014	Through synergistic induction of PIK3IP1 and inhibition of PI3K-AKT activation, prolonged early G1 arrest induced by PD 0332991 (palbociclib) inhibition of CDK4 sensitized resistant lymphoma cells to ibrutinib killing when BTK was unmutated, and to PI3K inhibitors independent of C481S mutation.	ibrutinib	200-209	phosphoinositide-3-kinase interacting protein 1	Homo sapiens	33-40
25082755-7	2014	SIGNIFICANCE: We have discovered the first relapse-specific BTK mutation in patients with MCL with acquired resistance, but not primary resistance, to ibrutinib, and demonstrated a rationale for targeting the proliferative resistant MCL cells by inhibiting CDK4 and the cell cycle in combination with ibrutinib in the presence of BTK(WT) or a PI3K inhibitor independent of BTK mutation.	ibrutinib	301-310	Bruton tyrosine kinase	Homo sapiens	330-333
25082755-7	2014	SIGNIFICANCE: We have discovered the first relapse-specific BTK mutation in patients with MCL with acquired resistance, but not primary resistance, to ibrutinib, and demonstrated a rationale for targeting the proliferative resistant MCL cells by inhibiting CDK4 and the cell cycle in combination with ibrutinib in the presence of BTK(WT) or a PI3K inhibitor independent of BTK mutation.	ibrutinib	301-310	Bruton tyrosine kinase	Homo sapiens	330-333
25082755-5	2014	Through synergistic induction of PIK3IP1 and inhibition of PI3K-AKT activation, prolonged early G1 arrest induced by PD 0332991 (palbociclib) inhibition of CDK4 sensitized resistant lymphoma cells to ibrutinib killing when BTK was unmutated, and to PI3K inhibitors independent of C481S mutation.	ibrutinib	200-209	cyclin dependent kinase 4	Homo sapiens	156-160
25150798-1	2014	BACKGROUND: Ibrutinib, an orally administered covalent inhibitor of Bruton"s tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	68-92
25082755-7	2014	SIGNIFICANCE: We have discovered the first relapse-specific BTK mutation in patients with MCL with acquired resistance, but not primary resistance, to ibrutinib, and demonstrated a rationale for targeting the proliferative resistant MCL cells by inhibiting CDK4 and the cell cycle in combination with ibrutinib in the presence of BTK(WT) or a PI3K inhibitor independent of BTK mutation.	ibrutinib	151-160	Bruton tyrosine kinase	Homo sapiens	60-63
25082755-7	2014	SIGNIFICANCE: We have discovered the first relapse-specific BTK mutation in patients with MCL with acquired resistance, but not primary resistance, to ibrutinib, and demonstrated a rationale for targeting the proliferative resistant MCL cells by inhibiting CDK4 and the cell cycle in combination with ibrutinib in the presence of BTK(WT) or a PI3K inhibitor independent of BTK mutation.	ibrutinib	151-160	cyclin dependent kinase 4	Homo sapiens	257-261
25082755-7	2014	SIGNIFICANCE: We have discovered the first relapse-specific BTK mutation in patients with MCL with acquired resistance, but not primary resistance, to ibrutinib, and demonstrated a rationale for targeting the proliferative resistant MCL cells by inhibiting CDK4 and the cell cycle in combination with ibrutinib in the presence of BTK(WT) or a PI3K inhibitor independent of BTK mutation.	ibrutinib	151-160	Bruton tyrosine kinase	Homo sapiens	330-333
25082755-7	2014	SIGNIFICANCE: We have discovered the first relapse-specific BTK mutation in patients with MCL with acquired resistance, but not primary resistance, to ibrutinib, and demonstrated a rationale for targeting the proliferative resistant MCL cells by inhibiting CDK4 and the cell cycle in combination with ibrutinib in the presence of BTK(WT) or a PI3K inhibitor independent of BTK mutation.	ibrutinib	151-160	Bruton tyrosine kinase	Homo sapiens	330-333
25082755-7	2014	SIGNIFICANCE: We have discovered the first relapse-specific BTK mutation in patients with MCL with acquired resistance, but not primary resistance, to ibrutinib, and demonstrated a rationale for targeting the proliferative resistant MCL cells by inhibiting CDK4 and the cell cycle in combination with ibrutinib in the presence of BTK(WT) or a PI3K inhibitor independent of BTK mutation.	ibrutinib	301-310	Bruton tyrosine kinase	Homo sapiens	60-63
25150798-1	2014	BACKGROUND: Ibrutinib, an orally administered covalent inhibitor of Bruton"s tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	94-97
25042202-0	2014	Combination of ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment-naive patients with CD20-positive B-cell non-Hodgkin lymphoma: a non-randomised, phase 1b study.	ibrutinib	15-24	DNA damage inducible transcript 3	Homo sapiens	103-107
24445187-3	2014	Ibrutinib, a novel first-in-human Bruton"s tyrosine kinase (BTK) inhibitor, has progressed into phase III trials after early-phase clinical studies demonstrated effective target inhibition, increased tumor response rates, and significant improvement in survival, particularly in patients with indolent B-cell lymphomas.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	34-58
24445187-3	2014	Ibrutinib, a novel first-in-human Bruton"s tyrosine kinase (BTK) inhibitor, has progressed into phase III trials after early-phase clinical studies demonstrated effective target inhibition, increased tumor response rates, and significant improvement in survival, particularly in patients with indolent B-cell lymphomas.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	60-63
25042202-0	2014	Combination of ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment-naive patients with CD20-positive B-cell non-Hodgkin lymphoma: a non-randomised, phase 1b study.	ibrutinib	15-24	keratin 20	Homo sapiens	143-147
25042202-2	2014	Ibrutinib, a novel oral Bruton"s tyrosine kinase inhibitor, has shown single-drug activity in relapsed or refractory B-cell malignancies.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	24-48
25042202-3	2014	We investigated the safety and efficacy of ibrutinib in combination with R-CHOP for patients with previously untreated CD20-positive B-cell non-Hodgkin lymphoma.	ibrutinib	43-52	keratin 20	Homo sapiens	119-123
25042202-21	2014	INTERPRETATION: Ibrutinib is well tolerated when added to R-CHOP, and could improve responses in patients with B-cell non-Hodgkin lymphoma, but our findings need confirmation in a phase 3 trial.	ibrutinib	16-25	DNA damage inducible transcript 3	Homo sapiens	60-64
25360238-0	2014	Bruton"s tyrosine kinase inhibitors and their clinical potential in the treatment of B-cell malignancies: focus on ibrutinib.	ibrutinib	115-124	Bruton tyrosine kinase	Homo sapiens	0-24
25360238-3	2014	Ibrutinib, the most clinically advanced small molecule inhibitor of BTK, has demonstrated impressive tolerability and activity in a range of B-cell lymphomas which led to its recent approval for relapsed mantle cell lymphoma and chronic lymphocytic leukemia.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	68-71
24697238-0	2014	The bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) blocks hairy cell leukaemia survival, proliferation and B cell receptor signalling: a new therapeutic approach.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	4-26
24970801-2	2014	Using in vitro screening, we have identified the combination of ibrutinib, an inhibitor of the tyrosine kinase BTK, and AZD2014, an mTOR catalytic inhibitor, as being highly synergistic in killing ABC-subtype DLBCL cell lines.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	111-114
24749490-5	2014	Clinically, the furthest in development is ibrutinib (trade name, Imbruvica), an irreversible BTKi, which has shown spectacular preliminary efficacy, with rapid reductions in lymph nodes accompanied by peripheral blood lymphocytosis.	ibrutinib	43-52	inhibitor of Bruton tyrosine kinase	Homo sapiens	94-98
25026208-1	2014	Ibrutinib is a potent inhibitor of Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	35-59
25026208-1	2014	Ibrutinib is a potent inhibitor of Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	61-64
24697238-2	2014	Bruton tyrosine kinase (BTK), a key player in BCR signalling, as well as B cell migration and adhesion, can be targeted with ibrutinib, a selective, irreversible BTK inhibitor.	ibrutinib	125-134	Bruton tyrosine kinase	Homo sapiens	0-22
24697238-2	2014	Bruton tyrosine kinase (BTK), a key player in BCR signalling, as well as B cell migration and adhesion, can be targeted with ibrutinib, a selective, irreversible BTK inhibitor.	ibrutinib	125-134	Bruton tyrosine kinase	Homo sapiens	24-27
24697238-2	2014	Bruton tyrosine kinase (BTK), a key player in BCR signalling, as well as B cell migration and adhesion, can be targeted with ibrutinib, a selective, irreversible BTK inhibitor.	ibrutinib	125-134	Bruton tyrosine kinase	Homo sapiens	162-165
24697238-7	2014	Ibrutinib also inhibited BCR-dependent secretion of the chemokines CCL3 and CCL4 by HCL cells.	ibrutinib	0-9	C-C motif chemokine ligand 3	Homo sapiens	67-71
24697238-7	2014	Ibrutinib also inhibited BCR-dependent secretion of the chemokines CCL3 and CCL4 by HCL cells.	ibrutinib	0-9	C-C motif chemokine ligand 4	Homo sapiens	76-80
24697238-8	2014	Interestingly, ibrutinib inhibited also CXCL12-induced signalling, a key pathway for bone marrow homing.	ibrutinib	15-24	C-X-C motif chemokine ligand 12	Homo sapiens	40-46
24481980-3	2014	The oral Bruton"s tyrosine kinase (BTK) inhibitor, ibrutinib, targets the B-cell receptor (BCR) signaling pathway that is critical in the survival of these malignancies.	ibrutinib	51-60	Bruton tyrosine kinase	Homo sapiens	9-33
24915291-2	2014	Ibrutinib is a first-in-class covalent irreversible Btk inhibitor and has demonstrated impressive effects in multiple clinical trials.	ibrutinib	0-9	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	52-55
24915291-4	2014	Compared with ibrutinib, these inhibitors exhibited a different selectivity profile for the analyzed kinases as well as a dual-action mode of inhibition of both Btk activation and catalytic activity, which counteracts a negative regulation loop for Btk.	ibrutinib	14-23	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	161-164
24915291-4	2014	Compared with ibrutinib, these inhibitors exhibited a different selectivity profile for the analyzed kinases as well as a dual-action mode of inhibition of both Btk activation and catalytic activity, which counteracts a negative regulation loop for Btk.	ibrutinib	14-23	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	249-252
24869598-0	2014	Resistance mechanisms for the Bruton"s tyrosine kinase inhibitor ibrutinib.	ibrutinib	65-74	Bruton tyrosine kinase	Homo sapiens	30-54
24869598-1	2014	BACKGROUND: Ibrutinib is an irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and is effective in chronic lymphocytic leukemia (CLL).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	54-78
24869598-1	2014	BACKGROUND: Ibrutinib is an irreversible inhibitor of Bruton"s tyrosine kinase (BTK) and is effective in chronic lymphocytic leukemia (CLL).	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	80-83
24869598-8	2014	RESULTS: We identified a cysteine-to-serine mutation in BTK at the binding site of ibrutinib in five patients and identified three distinct mutations in PLCgamma2 in two patients.	ibrutinib	83-92	Bruton tyrosine kinase	Homo sapiens	56-59
24869598-9	2014	Functional analysis showed that the C481S mutation of BTK results in a protein that is only reversibly inhibited by ibrutinib.	ibrutinib	116-125	Bruton tyrosine kinase	Homo sapiens	54-57
24869598-12	2014	CONCLUSIONS: Resistance to the irreversible BTK inhibitor ibrutinib often involves mutation of a cysteine residue where ibrutinib binding occurs.	ibrutinib	58-67	Bruton tyrosine kinase	Homo sapiens	44-47
24869598-12	2014	CONCLUSIONS: Resistance to the irreversible BTK inhibitor ibrutinib often involves mutation of a cysteine residue where ibrutinib binding occurs.	ibrutinib	120-129	Bruton tyrosine kinase	Homo sapiens	44-47
24869598-13	2014	This finding, combined with two additional mutations in PLCgamma2 that are immediately downstream of BTK, underscores the importance of the B-cell-receptor pathway in the mechanism of action of ibrutinib in CLL.	ibrutinib	194-203	phospholipase C gamma 2	Homo sapiens	56-65
24869598-13	2014	This finding, combined with two additional mutations in PLCgamma2 that are immediately downstream of BTK, underscores the importance of the B-cell-receptor pathway in the mechanism of action of ibrutinib in CLL.	ibrutinib	194-203	Bruton tyrosine kinase	Homo sapiens	101-104
24829205-0	2014	Kinetics of CLL cells in tissues and blood during therapy with the BTK inhibitor ibrutinib.	ibrutinib	81-90	Bruton tyrosine kinase	Homo sapiens	67-70
24829205-1	2014	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has excellent clinical activity in patients with chronic lymphocytic leukemia (CLL).	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	4-26
24829205-1	2014	The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has excellent clinical activity in patients with chronic lymphocytic leukemia (CLL).	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	28-31
24778403-4	2014	Ibrutinib (PCI-32765) is the most advanced BTK inhibitor in clinical testing, with ongoing phase III clinical trials in patients with chronic lymphocytic leukemia and mantle-cell lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	43-46
24481980-3	2014	The oral Bruton"s tyrosine kinase (BTK) inhibitor, ibrutinib, targets the B-cell receptor (BCR) signaling pathway that is critical in the survival of these malignancies.	ibrutinib	51-60	Bruton tyrosine kinase	Homo sapiens	35-38
24918646-1	2014	Ibrutinib is a novel oral tyrosine kinase inhibitor that irreversibly binds and inhibits tyrosine-protein kinase BTK (Bruton tyrosine kinase).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	113-116
24612681-9	2014	The important role of BTK in human DC activation was confirmed after incubation of healthy DCs with ibrutinib, the specific BTK inhibitor, which resulted in impairment of TLR9 responses as seen in patients with XLA.	ibrutinib	100-109	Bruton tyrosine kinase	Homo sapiens	22-25
24612681-9	2014	The important role of BTK in human DC activation was confirmed after incubation of healthy DCs with ibrutinib, the specific BTK inhibitor, which resulted in impairment of TLR9 responses as seen in patients with XLA.	ibrutinib	100-109	Bruton tyrosine kinase	Homo sapiens	124-127
24612681-9	2014	The important role of BTK in human DC activation was confirmed after incubation of healthy DCs with ibrutinib, the specific BTK inhibitor, which resulted in impairment of TLR9 responses as seen in patients with XLA.	ibrutinib	100-109	toll like receptor 9	Homo sapiens	171-175
24659631-6	2014	Ibrutinib significantly decreased tumor proliferation and expression of surface activation markers CD69 and CD86, independent of prognostic factors such as IGHV mutational status, chromosome 17p deletion, or prior treatment history.	ibrutinib	0-9	CD69 molecule	Homo sapiens	99-103
24659631-6	2014	Ibrutinib significantly decreased tumor proliferation and expression of surface activation markers CD69 and CD86, independent of prognostic factors such as IGHV mutational status, chromosome 17p deletion, or prior treatment history.	ibrutinib	0-9	CD86 molecule	Homo sapiens	108-112
24659631-7	2014	Interestingly, stronger inhibition of BCR signaling in lymph node resident CLL cells after one dose of ibrutinib was associated with a higher rate of nodal response at the end of cycle 2.	ibrutinib	103-112	BCR activator of RhoGEF and GTPase	Homo sapiens	38-41
24693884-2	2014	Recently Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib showed promising therapeutic effect in relapsed/refractory CLL and B-cell NHL, which provided essential alternatives for these patients.	ibrutinib	50-59	Bruton tyrosine kinase	Homo sapiens	9-33
24693884-2	2014	Recently Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib showed promising therapeutic effect in relapsed/refractory CLL and B-cell NHL, which provided essential alternatives for these patients.	ibrutinib	50-59	Bruton tyrosine kinase	Homo sapiens	35-38
24693884-5	2014	RESULTS: We demonstrated that ibrutinib inhibited the proliferation and induced apoptosis of GCB-DLBCL cell lines through suppression of BCR signaling pathway and activation of caspase-3.	ibrutinib	30-39	caspase 3	Homo sapiens	177-186
24693884-6	2014	Furthermore, the chemokines CCL3 and CCL4 production from tumor cells were also found to be attenuated by ibrutinib treatment.	ibrutinib	106-115	C-C motif chemokine ligand 3	Homo sapiens	28-32
24693884-6	2014	Furthermore, the chemokines CCL3 and CCL4 production from tumor cells were also found to be attenuated by ibrutinib treatment.	ibrutinib	106-115	C-C motif chemokine ligand 4	Homo sapiens	37-41
24693884-8	2014	Interestingly, the decreasing level of p-ERK after ibrutinib treatment, but not the basal expression level of Btk, correlated with different drug sensitivity.	ibrutinib	51-60	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	39-44
24812669-8	2014	Additionally, B-I09 and ibrutinib, an FDA-approved BTK inhibitor, synergized to induce apoptosis in B cell leukemia, lymphoma, and multiple myeloma.	ibrutinib	24-33	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	51-54
24659631-0	2014	Ibrutinib inhibits BCR and NF-kappaB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL.	ibrutinib	0-9	BCR activator of RhoGEF and GTPase	Homo sapiens	19-22
24659631-3	2014	We evaluated the in vivo effects of ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor on tumor cell activation and proliferation in the blood, lymph node, and bone marrow of patients with CLL.	ibrutinib	36-45	Bruton tyrosine kinase	Homo sapiens	73-76
24659631-4	2014	Applying validated pathway-specific gene signatures, we detected a rapid and sustained downregulation of BCR and NF-kappaB signaling in CLL cells from both the peripheral blood and tissue compartments during ibrutinib treatment.	ibrutinib	208-217	BCR activator of RhoGEF and GTPase	Homo sapiens	105-108
24659631-5	2014	Ibrutinib reduced phosphorylation of PLCgamma2 and ERK and decreased nuclear protein expression of NF-kappaB p50.	ibrutinib	0-9	phospholipase C gamma 2	Homo sapiens	37-46
24659631-5	2014	Ibrutinib reduced phosphorylation of PLCgamma2 and ERK and decreased nuclear protein expression of NF-kappaB p50.	ibrutinib	0-9	EPH receptor B2	Homo sapiens	51-54
24659631-5	2014	Ibrutinib reduced phosphorylation of PLCgamma2 and ERK and decreased nuclear protein expression of NF-kappaB p50.	ibrutinib	0-9	nuclear factor kappa B subunit 1	Homo sapiens	99-112
24759210-2	2014	We synthesized a fluorescent, irreversible BTK binder based on the drug Ibrutinib and characterized its behavior in cells and in vivo.	ibrutinib	72-81	Bruton tyrosine kinase	Homo sapiens	43-46
24918646-1	2014	Ibrutinib is a novel oral tyrosine kinase inhibitor that irreversibly binds and inhibits tyrosine-protein kinase BTK (Bruton tyrosine kinase).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	118-140
24918646-3	2014	Targeting BTK with ibrutinib has been found to be an effective strategy in treating these malignancies.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	10-13
24895895-6	2014	Ibrutinib won the US FDA approval in November 2013 to become the first-in-class BTK inhibitor for treating mantle cell lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	80-83
24316417-0	2014	The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss.	ibrutinib	35-44	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	21-24
24415539-1	2014	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has outstanding activity in patients with chronic lymphocytic leukemia.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	4-28
24415539-1	2014	The Bruton"s tyrosine kinase (BTK) inhibitor ibrutinib has outstanding activity in patients with chronic lymphocytic leukemia.	ibrutinib	45-54	Bruton tyrosine kinase	Homo sapiens	30-33
24316417-3	2014	Here we demonstrate that an orally available Btk inhibitor, ibrutinib (PCI-32765), suppresses osteoclastic bone resorption by inhibiting both osteoclast differentiation and function.	ibrutinib	60-69	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	45-48
24316417-4	2014	Ibrutinib downregulated the expression of NFATc1, the key transcription factor for osteoclastogenesis, and disrupted the formation of the actin ring in mature osteoclasts.	ibrutinib	0-9	nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1	Mus musculus	42-48
24316417-6	2014	Finally, we showed that ibrutinib administration ameliorated the bone loss that developed in a RANKL-induced osteoporosis mouse model.	ibrutinib	24-33	tumor necrosis factor (ligand) superfamily, member 11	Mus musculus	95-100
24338680-0	2014	The promising impact of ibrutinib, a Bruton"s tyrosine kinase inhibitor, for the management of lymphoid malignancies.	ibrutinib	24-33	Bruton tyrosine kinase	Homo sapiens	37-61
24357428-3	2014	The BTK inhibitor ibrutinib (PCI-32765, brand name: Imbruvica) demonstrated high clinical activity in B-cell malignancies, especially in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenstrom"s macroglobulinemia (WM).	ibrutinib	18-27	Bruton tyrosine kinase	Homo sapiens	4-7
24357428-3	2014	The BTK inhibitor ibrutinib (PCI-32765, brand name: Imbruvica) demonstrated high clinical activity in B-cell malignancies, especially in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenstrom"s macroglobulinemia (WM).	ibrutinib	29-38	Bruton tyrosine kinase	Homo sapiens	4-7
24357428-3	2014	The BTK inhibitor ibrutinib (PCI-32765, brand name: Imbruvica) demonstrated high clinical activity in B-cell malignancies, especially in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenstrom"s macroglobulinemia (WM).	ibrutinib	52-61	Bruton tyrosine kinase	Homo sapiens	4-7
24338680-4	2014	At the forefront of clinical development is ibrutinib, an inhibitor of Bruton"s tyrosine kinase (Btk).	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	71-95
24338680-4	2014	At the forefront of clinical development is ibrutinib, an inhibitor of Bruton"s tyrosine kinase (Btk).	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	97-100
24323900-7	2014	Here, we review central components of the CLL microenvironment, with a particular emphasis on BCR signaling, and we summarize the most relevant clinical advances with inhibitors that target the BCR-associated spleen tyrosine kinase/SYK (fostamatinib), Bruton"s tyrosine kinase/BTK (ibrutinib), and PI3Kdelta (idelalisib).	ibrutinib	282-291	BCR activator of RhoGEF and GTPase	Homo sapiens	194-197
24307721-3	2014	Pharmacologic targeting of BTK using ibrutinib (previously PCI-32765) has recently shown encouraging clinical activity in a range of lymphoid malignancies.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	27-30
24307721-5	2014	Here we describe that BTK is constitutively phosphorylated in the majority of AML samples tested, with BTK phosphorylation correlating highly with the cell"s cytotoxic sensitivity toward ibrutinib.	ibrutinib	187-196	Bruton tyrosine kinase	Homo sapiens	22-25
24307721-5	2014	Here we describe that BTK is constitutively phosphorylated in the majority of AML samples tested, with BTK phosphorylation correlating highly with the cell"s cytotoxic sensitivity toward ibrutinib.	ibrutinib	187-196	Bruton tyrosine kinase	Homo sapiens	103-106
24307721-7	2014	We showed that ibrutinib binds at nanomolar range to BTK.	ibrutinib	15-24	Bruton tyrosine kinase	Homo sapiens	53-56
24311722-2	2014	Bruton"s tyrosine kinase (BTK) shows constitutive activity in CLL and is the target of irreversible inhibition by ibrutinib, an orally bioavailable kinase inhibitor that has shown outstanding activity in CLL.	ibrutinib	114-123	Bruton tyrosine kinase	Homo sapiens	0-24
24311722-2	2014	Bruton"s tyrosine kinase (BTK) shows constitutive activity in CLL and is the target of irreversible inhibition by ibrutinib, an orally bioavailable kinase inhibitor that has shown outstanding activity in CLL.	ibrutinib	114-123	Bruton tyrosine kinase	Homo sapiens	26-29
24311722-6	2014	Inhibition of BTK kinase activity through either targeted genetic inactivation or ibrutinib in the TCL1 mouse significantly delays the development of CLL, demonstrating that BTK is a critical kinase for CLL development and expansion and thus an important target of ibrutinib.	ibrutinib	82-91	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	14-17
24311722-6	2014	Inhibition of BTK kinase activity through either targeted genetic inactivation or ibrutinib in the TCL1 mouse significantly delays the development of CLL, demonstrating that BTK is a critical kinase for CLL development and expansion and thus an important target of ibrutinib.	ibrutinib	82-91	T cell lymphoma breakpoint 1	Mus musculus	99-103
24311722-6	2014	Inhibition of BTK kinase activity through either targeted genetic inactivation or ibrutinib in the TCL1 mouse significantly delays the development of CLL, demonstrating that BTK is a critical kinase for CLL development and expansion and thus an important target of ibrutinib.	ibrutinib	265-274	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	14-17
24311722-6	2014	Inhibition of BTK kinase activity through either targeted genetic inactivation or ibrutinib in the TCL1 mouse significantly delays the development of CLL, demonstrating that BTK is a critical kinase for CLL development and expansion and thus an important target of ibrutinib.	ibrutinib	265-274	T cell lymphoma breakpoint 1	Mus musculus	99-103
24311722-6	2014	Inhibition of BTK kinase activity through either targeted genetic inactivation or ibrutinib in the TCL1 mouse significantly delays the development of CLL, demonstrating that BTK is a critical kinase for CLL development and expansion and thus an important target of ibrutinib.	ibrutinib	265-274	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	174-177
24323900-7	2014	Here, we review central components of the CLL microenvironment, with a particular emphasis on BCR signaling, and we summarize the most relevant clinical advances with inhibitors that target the BCR-associated spleen tyrosine kinase/SYK (fostamatinib), Bruton"s tyrosine kinase/BTK (ibrutinib), and PI3Kdelta (idelalisib).	ibrutinib	282-291	spleen associated tyrosine kinase	Homo sapiens	232-235
24332241-2	2014	We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia.	ibrutinib	42-51	inhibitor of Bruton tyrosine kinase	Homo sapiens	85-120
24472371-3	2014	Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site of BTK (TH/SH1 domain) and inhibits BTK phosphorylation on Tyr223.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	45-48
24472371-3	2014	Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site of BTK (TH/SH1 domain) and inhibits BTK phosphorylation on Tyr223.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	167-170
24472371-3	2014	Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site of BTK (TH/SH1 domain) and inhibits BTK phosphorylation on Tyr223.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	167-170
23656200-1	2014	Recent clinical data suggest remarkable activity of ibrutinib, the first-in-class covalent inhibitor of Bruton"s tyrosine kinase (BTK), in chronic lymphocytic leukemia (CLL), as well as excellent activity in other B cell malignancies, including in particular mantle cell lymphoma and Waldenstrom macroglobulinemia.	ibrutinib	52-61	Bruton tyrosine kinase	Homo sapiens	104-128
23656200-1	2014	Recent clinical data suggest remarkable activity of ibrutinib, the first-in-class covalent inhibitor of Bruton"s tyrosine kinase (BTK), in chronic lymphocytic leukemia (CLL), as well as excellent activity in other B cell malignancies, including in particular mantle cell lymphoma and Waldenstrom macroglobulinemia.	ibrutinib	52-61	Bruton tyrosine kinase	Homo sapiens	130-133
24598688-2	2014	Ibrutinib is a novel and selective inhibitor of BTK, inactivating the kinase irreversibly.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	48-51
24472371-5	2014	Clinical trials of the novel BTK inhibitor, ibrutinib (PCI-32765), in B cell malignancies were summarized.	ibrutinib	44-53	Bruton tyrosine kinase	Homo sapiens	29-32
24332241-2	2014	We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia.	ibrutinib	42-51	Bruton tyrosine kinase	Homo sapiens	122-125
24362935-4	2014	Transcriptome sequencing revealed genetic lesions in alternative NF-kappaB pathway signaling components in ibrutinib-insensitive cell lines, and sequencing of 165 samples from patients with MCL identified recurrent mutations in TRAF2 or BIRC3 in 15% of these individuals.	ibrutinib	107-116	nuclear factor kappa B subunit 1	Homo sapiens	65-74
24362935-5	2014	Although they are associated with insensitivity to ibrutinib, lesions in the alternative NF-kappaB pathway conferred dependence on the protein kinase NIK (also called mitogen-activated protein 3 kinase 14 or MAP3K14) both in vitro and in vivo.	ibrutinib	51-60	nuclear factor kappa B subunit 1	Homo sapiens	89-98
24756799-3	2014	Ibrutinib (PCI-32765) is a novel agent which serves as a covalent irreversible inhibitor of BTK.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	92-95
24111579-3	2013	There are several BTK inhibitors, including ONO-WG-307, LFM-A13, dasatinib, CC-292, and PCI-32765 (ibrutinib), in preclinical and/or clinical development of which ibrutinib is currently in phase III trials.	ibrutinib	99-108	Bruton tyrosine kinase	Homo sapiens	18-21
24433470-0	2013	Ibrutinib: a new frontier in the treatment of chronic lymphocytic leukemia by Bruton"s tyrosine kinase inhibition.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	78-102
24433470-8	2013	Ibrutinib is an oral covalent inhibitor of the BTK pathway that induces apoptosis of B cells.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	47-50
23619564-7	2013	Next, we used this model to study ibrutinib, a Bruton"s tyrosine kinase inhibitor in clinical development.	ibrutinib	34-43	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	47-71
24009233-9	2013	Furthermore, we demonstrate that the Bruton"s tyrosine kinase inhibitor ibrutinib or the PI3K inhibitor idelalisib block B-cell receptor induced activation of LCP1.	ibrutinib	72-81	lymphocyte cytosolic protein 1	Homo sapiens	159-163
24111579-3	2013	There are several BTK inhibitors, including ONO-WG-307, LFM-A13, dasatinib, CC-292, and PCI-32765 (ibrutinib), in preclinical and/or clinical development of which ibrutinib is currently in phase III trials.	ibrutinib	163-172	Bruton tyrosine kinase	Homo sapiens	18-21
24111579-4	2013	Recent clinical data suggest significant activity of ibrutinib as a first in class oral inhibitor of BTK.	ibrutinib	53-62	Bruton tyrosine kinase	Homo sapiens	101-104
24103588-6	2013	Currently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, which acts downstream the BCR signaling pathway, appears to be particularly promising and shows important clinical activity in CLL.	ibrutinib	54-63	Bruton tyrosine kinase	Homo sapiens	15-37
24085367-7	2013	Ibrutinib acts by inhibiting the Bruton"s tyrosine kinase (BTK) while idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	33-57
24085367-7	2013	Ibrutinib acts by inhibiting the Bruton"s tyrosine kinase (BTK) while idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	59-62
23962569-0	2013	Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by Ibrutinib induces apoptosis.	ibrutinib	96-105	Bruton tyrosine kinase	Homo sapiens	0-22
23962569-8	2013	Treatment of MCL cell lines (Mino or Jeko-1) with a potent BTK pharmacologic inhibitor, Ibrutinib, decreased phospho-BTK-Tyr(223) expression.	ibrutinib	88-97	Bruton tyrosine kinase	Homo sapiens	59-62
23962569-8	2013	Treatment of MCL cell lines (Mino or Jeko-1) with a potent BTK pharmacologic inhibitor, Ibrutinib, decreased phospho-BTK-Tyr(223) expression.	ibrutinib	88-97	Bruton tyrosine kinase	Homo sapiens	117-120
23962569-11	2013	Consistently, Ibrutinib treatment decreased the levels of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1 protein.	ibrutinib	14-23	BCL2 apoptosis regulator	Homo sapiens	73-78
23962569-11	2013	Consistently, Ibrutinib treatment decreased the levels of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1 protein.	ibrutinib	14-23	BCL2 like 1	Homo sapiens	80-86
23962569-11	2013	Consistently, Ibrutinib treatment decreased the levels of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1 protein.	ibrutinib	14-23	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	92-97
24156429-1	2013	This study was aimed to investigate the effect of Btk inhibitor PCI-32765 and the proteasome inhibitor bortezomib on Raji and Ramos cell proliferation, apoptosis, and its mechanisms.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	50-53
23954894-6	2013	Phosphorylation was suppressed by the BTK inhibitor ibrutinib.	ibrutinib	52-61	Bruton tyrosine kinase	Homo sapiens	38-41
23940282-0	2013	Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients.	ibrutinib	114-123	CD19 molecule	Homo sapiens	10-14
23940282-0	2013	Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients.	ibrutinib	114-123	Bruton tyrosine kinase	Homo sapiens	81-103
23940282-1	2013	Ibrutinib (PCI-32765) is a highly potent oral Bruton tyrosine kinase (BTK) inhibitor in clinical development for treating B-cell lymphoproliferative diseases.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	46-68
23940282-1	2013	Ibrutinib (PCI-32765) is a highly potent oral Bruton tyrosine kinase (BTK) inhibitor in clinical development for treating B-cell lymphoproliferative diseases.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	70-73
23940282-7	2013	Mechanistically, ibrutinib inhibited BCR- and chemokine-mediated adhesion and chemotaxis of MCL cell lines and dose-dependently inhibited BCR, stromal cell, and CXCL12/CXCL13 stimulations of pBTK, pPLCgamma2, pERK, or pAKT.	ibrutinib	17-26	C-X-C motif chemokine ligand 12	Homo sapiens	161-167
23940282-7	2013	Mechanistically, ibrutinib inhibited BCR- and chemokine-mediated adhesion and chemotaxis of MCL cell lines and dose-dependently inhibited BCR, stromal cell, and CXCL12/CXCL13 stimulations of pBTK, pPLCgamma2, pERK, or pAKT.	ibrutinib	17-26	C-X-C motif chemokine ligand 13	Homo sapiens	168-174
23940282-7	2013	Mechanistically, ibrutinib inhibited BCR- and chemokine-mediated adhesion and chemotaxis of MCL cell lines and dose-dependently inhibited BCR, stromal cell, and CXCL12/CXCL13 stimulations of pBTK, pPLCgamma2, pERK, or pAKT.	ibrutinib	17-26	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	209-213
24083545-1	2013	Drugs that selectively inhibit Bruton"s tyrosine kinase (BTK), such as the new orally administered agent ibrutinib, are currently under investigation for the treatment of several types of B-cell malignancies.	ibrutinib	105-114	Bruton tyrosine kinase	Homo sapiens	31-55
24083545-1	2013	Drugs that selectively inhibit Bruton"s tyrosine kinase (BTK), such as the new orally administered agent ibrutinib, are currently under investigation for the treatment of several types of B-cell malignancies.	ibrutinib	105-114	Bruton tyrosine kinase	Homo sapiens	57-60
24103588-6	2013	Currently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, which acts downstream the BCR signaling pathway, appears to be particularly promising and shows important clinical activity in CLL.	ibrutinib	54-63	Bruton tyrosine kinase	Homo sapiens	39-42
23782157-0	2013	Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	10-13
23958373-3	2013	Ibrutinib, a novel first-in-human BTK-inhibitor, has demonstrated clinical effectiveness and tolerability in early clinical trials and has progressed into phase III trials.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	34-37
23782157-2	2013	In a phase 1 study, ibrutinib, a BTK inhibitor, showed antitumor activity in several types of non-Hodgkin"s lymphoma, including mantle-cell lymphoma.	ibrutinib	20-29	Bruton tyrosine kinase	Homo sapiens	33-36
23360303-0	2013	The Bruton tyrosine kinase (BTK) inhibitor PCI-32765 synergistically increases proteasome inhibitor activity in diffuse large-B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells sensitive or resistant to bortezomib.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	4-26
23754751-8	2013	A newly characterized 14-3-3 inhibitor, BV02, reduced binding, as did the Btk inhibitor PCI-32765 (ibrutinib).	ibrutinib	88-97	Bruton tyrosine kinase	Homo sapiens	74-77
23754751-8	2013	A newly characterized 14-3-3 inhibitor, BV02, reduced binding, as did the Btk inhibitor PCI-32765 (ibrutinib).	ibrutinib	99-108	Bruton tyrosine kinase	Homo sapiens	74-77
23672610-6	2013	The newly developed BTK inhibitor PCI-32765, recently renamed Ibrutinib, has already entered several clinical trials for various forms of non-Hodgkin lymphoma as well as for multiple myeloma.	ibrutinib	34-43	Bruton tyrosine kinase	Homo sapiens	20-23
23672610-6	2013	The newly developed BTK inhibitor PCI-32765, recently renamed Ibrutinib, has already entered several clinical trials for various forms of non-Hodgkin lymphoma as well as for multiple myeloma.	ibrutinib	62-71	Bruton tyrosine kinase	Homo sapiens	20-23
23782158-0	2013	Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.	ibrutinib	19-28	Bruton tyrosine kinase	Homo sapiens	10-13
23360303-0	2013	The Bruton tyrosine kinase (BTK) inhibitor PCI-32765 synergistically increases proteasome inhibitor activity in diffuse large-B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells sensitive or resistant to bortezomib.	ibrutinib	43-52	Bruton tyrosine kinase	Homo sapiens	28-31
23360303-1	2013	Interactions between the Bruton tyrosine kinase (BTK) inhibitor PCI-32765 and the proteasome inhibitor (bortezomib) were examined in diffuse large-B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells, including those highly resistant to bortezomib.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	25-47
23360303-1	2013	Interactions between the Bruton tyrosine kinase (BTK) inhibitor PCI-32765 and the proteasome inhibitor (bortezomib) were examined in diffuse large-B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells, including those highly resistant to bortezomib.	ibrutinib	64-73	Bruton tyrosine kinase	Homo sapiens	49-52
23296407-0	2013	Ibrutinib (PCI-32765), the first BTK (Bruton"s tyrosine kinase) inhibitor in clinical trials.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	33-36
23296407-0	2013	Ibrutinib (PCI-32765), the first BTK (Bruton"s tyrosine kinase) inhibitor in clinical trials.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	38-62
23296407-1	2013	Ibrutinib is a potent covalent kinase inhibitor that targets BTK.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	61-64
23045577-0	2013	Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	0-22
24014301-5	2013	In particular, the BTK inhibitor ibrutinib and the PI3K inhibitor idelalisib (GS-1101) are two evolving targeted therapies with the most mature clinical data.	ibrutinib	33-42	Bruton tyrosine kinase	Homo sapiens	19-22
23359016-3	2013	While first studies on the selective small molecule inhibitor of Bruton"s tyrosine kinase (Btk), Ibrutinib (PCI-32765), demonstrated that Btk inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior, these studies however did not address whether Btk-mediated signaling is involved in the process of CLL leukemogenesis.	ibrutinib	97-106	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	65-89
23359016-3	2013	While first studies on the selective small molecule inhibitor of Bruton"s tyrosine kinase (Btk), Ibrutinib (PCI-32765), demonstrated that Btk inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior, these studies however did not address whether Btk-mediated signaling is involved in the process of CLL leukemogenesis.	ibrutinib	97-106	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	91-94
23359016-3	2013	While first studies on the selective small molecule inhibitor of Bruton"s tyrosine kinase (Btk), Ibrutinib (PCI-32765), demonstrated that Btk inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior, these studies however did not address whether Btk-mediated signaling is involved in the process of CLL leukemogenesis.	ibrutinib	97-106	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	138-141
23359016-3	2013	While first studies on the selective small molecule inhibitor of Bruton"s tyrosine kinase (Btk), Ibrutinib (PCI-32765), demonstrated that Btk inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior, these studies however did not address whether Btk-mediated signaling is involved in the process of CLL leukemogenesis.	ibrutinib	97-106	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	138-141
22975686-0	2013	BTK inhibitor ibrutinib is cytotoxic to myeloma and potently enhances bortezomib and lenalidomide activities through NF-kappaB.	ibrutinib	14-23	Bruton tyrosine kinase	Homo sapiens	0-3
22975686-1	2013	Ibrutinib (previously known as PCI-32765) has recently shown encouraging clinical activity in chronic lymphocytic leukaemia (CLL) effecting cell death through inhibition of Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	173-197
22975686-1	2013	Ibrutinib (previously known as PCI-32765) has recently shown encouraging clinical activity in chronic lymphocytic leukaemia (CLL) effecting cell death through inhibition of Bruton"s tyrosine kinase (BTK).	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	199-202
22975686-4	2013	Specifically, ibrutinib blocks the phosphorylation of serine-536 of the p65 subunit of NF-kappaB, preventing its nuclear translocation, resulting in down-regulation of anti-apoptotic proteins Bcl-xL, FLIP(L) and survivin and culminating in caspase-mediated apoptosis within the malignant plasma cells.	ibrutinib	14-23	RELA proto-oncogene, NF-kB subunit	Homo sapiens	72-96
22975686-4	2013	Specifically, ibrutinib blocks the phosphorylation of serine-536 of the p65 subunit of NF-kappaB, preventing its nuclear translocation, resulting in down-regulation of anti-apoptotic proteins Bcl-xL, FLIP(L) and survivin and culminating in caspase-mediated apoptosis within the malignant plasma cells.	ibrutinib	14-23	BCL2 like 1	Homo sapiens	192-198
23045577-2	2013	We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies.	ibrutinib	13-22	Bruton tyrosine kinase	Homo sapiens	79-82
23045577-5	2013	Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe.	ibrutinib	20-29	Bruton tyrosine kinase	Homo sapiens	13-16
23045577-15	2013	CONCLUSION: Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.	ibrutinib	12-21	Bruton tyrosine kinase	Homo sapiens	31-34
23763320-3	2013	Recently published results of clinical trials of three different molecules (fosfamatinib, ibrutinib and GS 1101) targeting BCRassociated kinases (Syk, Btk, PI3K) showed impressive clinical activity in CLL.	ibrutinib	90-99	spleen associated tyrosine kinase	Homo sapiens	146-149
23763320-3	2013	Recently published results of clinical trials of three different molecules (fosfamatinib, ibrutinib and GS 1101) targeting BCRassociated kinases (Syk, Btk, PI3K) showed impressive clinical activity in CLL.	ibrutinib	90-99	Bruton tyrosine kinase	Homo sapiens	151-154
21782064-6	2011	Promising results with the BTK inhibitor PCI-32765 suggest that B-cell receptor signaling could play a role.	ibrutinib	41-50	Bruton tyrosine kinase	Homo sapiens	27-30
22279054-0	2012	The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia.	ibrutinib	36-45	Bruton tyrosine kinase	Homo sapiens	22-25
22279054-2	2012	These agents, including the Bruton tyrosine kinase (BTK) inhibitor PCI-32765, display an unexpected response in patients with chronic lymphocytic leukemia (CLL): a rapid and sustained reduction of lymphadenopathy accompanied by transient lymphocytosis, which is reversible upon temporary drug deprivation.	ibrutinib	67-76	Bruton tyrosine kinase	Homo sapiens	28-50
22279054-2	2012	These agents, including the Bruton tyrosine kinase (BTK) inhibitor PCI-32765, display an unexpected response in patients with chronic lymphocytic leukemia (CLL): a rapid and sustained reduction of lymphadenopathy accompanied by transient lymphocytosis, which is reversible upon temporary drug deprivation.	ibrutinib	67-76	Bruton tyrosine kinase	Homo sapiens	52-55
22180443-2	2012	PCI-32765, a selective, irreversible Btk inhibitor, is a novel, molecularly targeted agent for patients with B-cell malignancies, and is particularly active in patients with CLL.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	37-40
21752263-0	2011	The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	4-26
21752263-1	2011	INTRODUCTION: The aim was to determine the effect of the Bruton tyrosine kinase (Btk)-selective inhibitor PCI-32765, currently in Phase I/II studies in lymphoma trials, in arthritis and immune-complex (IC) based animal models and describe the underlying cellular mechanisms.	ibrutinib	106-115	Bruton tyrosine kinase	Homo sapiens	57-79
21752263-1	2011	INTRODUCTION: The aim was to determine the effect of the Bruton tyrosine kinase (Btk)-selective inhibitor PCI-32765, currently in Phase I/II studies in lymphoma trials, in arthritis and immune-complex (IC) based animal models and describe the underlying cellular mechanisms.	ibrutinib	106-115	Bruton tyrosine kinase	Homo sapiens	81-84
21752263-11	2011	Following FcgammaR stimulation, PCI-32765 inhibited TNFalpha, IL-1beta and IL-6 production in primary monocytes (IC(50) = 2.6, 0.5, 3.9 nM, respectively).	ibrutinib	32-41	tumor necrosis factor	Homo sapiens	52-60
21752263-11	2011	Following FcgammaR stimulation, PCI-32765 inhibited TNFalpha, IL-1beta and IL-6 production in primary monocytes (IC(50) = 2.6, 0.5, 3.9 nM, respectively).	ibrutinib	32-41	interleukin 1 beta	Homo sapiens	62-70
21752263-11	2011	Following FcgammaR stimulation, PCI-32765 inhibited TNFalpha, IL-1beta and IL-6 production in primary monocytes (IC(50) = 2.6, 0.5, 3.9 nM, respectively).	ibrutinib	32-41	interleukin 6	Homo sapiens	75-79
23136880-5	2012	METHODS: B6.Sle1 or B6.Sle1.Sle3 mice received drinking water containing either the Btk inhibitor PCI-32765 or vehicle for 56 days.	ibrutinib	98-107	Bruton agammaglobulinemia tyrosine kinase	Mus musculus	84-87
22960555-10	2012	SUMMARY: Small molecule inhibitors of BCR signaling kinases, Bruton"s tyrosine kinase (Btk) inhibitor ibrutinib and the phosphoinositide 3"-kinase delta (PI3Kdelta) inhibitor GS-1101, are currently transforming the landscape of CLL therapy.	ibrutinib	102-111	Bruton tyrosine kinase	Homo sapiens	87-90
22698399-5	2012	Blockade of B cell receptor signaling using the BTK inhibitor ibrutinib also downregulates IRF4 and consequently synergizes with lenalidomide in killing ABC DLBCLs, suggesting attractive therapeutic strategies.	ibrutinib	62-71	Bruton tyrosine kinase	Homo sapiens	48-51
22698399-5	2012	Blockade of B cell receptor signaling using the BTK inhibitor ibrutinib also downregulates IRF4 and consequently synergizes with lenalidomide in killing ABC DLBCLs, suggesting attractive therapeutic strategies.	ibrutinib	62-71	interferon regulatory factor 4	Homo sapiens	91-95
22698399-5	2012	Blockade of B cell receptor signaling using the BTK inhibitor ibrutinib also downregulates IRF4 and consequently synergizes with lenalidomide in killing ABC DLBCLs, suggesting attractive therapeutic strategies.	ibrutinib	62-71	ATP binding cassette subfamily B member 6 (Langereis blood group)	Homo sapiens	153-156
22131884-6	2011	PCI-32765 is a novel inhibitor of Bruton tyrosine kinase (Btk) that blocks mast cell degranulation and is currently in clinical trial as a therapy for B-cell non-Hodgkin lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	34-56
22131884-6	2011	PCI-32765 is a novel inhibitor of Bruton tyrosine kinase (Btk) that blocks mast cell degranulation and is currently in clinical trial as a therapy for B-cell non-Hodgkin lymphoma.	ibrutinib	0-9	Bruton tyrosine kinase	Homo sapiens	58-61
22131884-8	2011	These data reinforce the notion that mast cell function is required for maintenance of certain tumor types and indicate that the Btk inhibitor PCI-32765 may be useful in treating such diseases.	ibrutinib	143-152	Bruton tyrosine kinase	Homo sapiens	129-132
21422473-5	2011	Using the irreversible BTK inhibitor PCI-32765, we demonstrate modest apoptosis in CLL cells that is greater than that observed in normal B cells.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	23-26
20615965-0	2010	The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy.	ibrutinib	37-46	Bruton tyrosine kinase	Homo sapiens	4-26