PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 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 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 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 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 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 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 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 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 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 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 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 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 33303706-1 2020 Background: Ibrutinib is an oral irreversible Bruton"s tyrosine kinase inhibitor. ibrutinib 12-21 Bruton tyrosine kinase Homo sapiens 46-70 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 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 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 32613545-6 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 Bruton tyrosine kinase Homo sapiens 100-103 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 32673127-4 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 Bruton tyrosine kinase Homo sapiens 135-138 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 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 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 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 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 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 18-42 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 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 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 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 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 32459810-8 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 32459810-11 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 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 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 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 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 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 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 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 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 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 32494164-7 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 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 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 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 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 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 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 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 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 32184360-1 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 31996046-2 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 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 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 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 31871305-5 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 31871305-8 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 31871305-10 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 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 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 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 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 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 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 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 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 Bruton tyrosine kinase Homo sapiens 66-69 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 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 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 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 31180577-7 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 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 31726100-7 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 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 31869418-1 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 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 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 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 Bruton tyrosine kinase Homo sapiens 71-74 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 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 31801949-2 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 31646085-11 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 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 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 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 58-80 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 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 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 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 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 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 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 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 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 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 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 31028669-0 2019 Targeting BTK in CLL: Beyond Ibrutinib. ibrutinib 29-38 Bruton tyrosine kinase Homo sapiens 10-13 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 Bruton tyrosine kinase Homo sapiens 121-124 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 Bruton tyrosine kinase Homo sapiens 15-18 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 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 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 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 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 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 30663221-1 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 30026342-5 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 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 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 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 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 30385492-0 2018 Ibrutinib and Aspergillus: a Btk-targeted risk. ibrutinib 0-9 Bruton tyrosine kinase Homo sapiens 29-32 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 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 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 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 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 30280589-2 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 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 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 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 34-58 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 < 0.001). ibrutinib 96-105 Bruton tyrosine kinase Homo sapiens 35-38 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 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 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 30190023-2 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 29743179-12 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 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 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 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 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 30030853-8 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 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 >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 >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 >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 >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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 29381098-6 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 237-246 Bruton tyrosine kinase Homo sapiens 25-28 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 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 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 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 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 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 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 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 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 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 29669753-2 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 Bruton tyrosine kinase Homo sapiens 142-145 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 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 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 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 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 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 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 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 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 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 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 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 28619981-10 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 27-30 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 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 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 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 27904138-2 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 27904138-6 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 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 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 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 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 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 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 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 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 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 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 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 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 28088788-1 2017 Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL. ibrutinib 0-9 Bruton tyrosine kinase Homo sapiens 11-14 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 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 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 4-26 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 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 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 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 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 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 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 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 27678331-2 2016 Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK. ibrutinib 0-9 Bruton tyrosine kinase Homo sapiens 66-69 27678331-9 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 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 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 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 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 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 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 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 27157620-10 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 27590878-2 2016 Ibrutinib is the first-generation BTK inhibitor. ibrutinib 0-9 Bruton tyrosine kinase Homo sapiens 34-37 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 27256378-4 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 27256378-11 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 27508020-0 2016 Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth. ibrutinib 19-28 Bruton tyrosine kinase Homo sapiens 10-13 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 27143257-3 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 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 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 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 Bruton tyrosine kinase Homo sapiens 33-36 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 26624983-7 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 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 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 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 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 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 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 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 26540570-6 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 Bruton tyrosine kinase Homo sapiens 68-71 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 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 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 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 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 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 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 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 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 25972157-4 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 25972157-8 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 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 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 25388373-7 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 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 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 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 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 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 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 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 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 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 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 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 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 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 26688095-10 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 26688095-12 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 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 Bruton tyrosine kinase Homo sapiens 48-72 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 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 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 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 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 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 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 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 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 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 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 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 Bruton tyrosine kinase Homo sapiens 19-22 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 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 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 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 25158606-5 2014 Ibrutinib is an orally active, Bruton"s tyrosine kinase inhibitor. ibrutinib 0-9 Bruton tyrosine kinase Homo sapiens 31-55 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 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 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 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 25294819-7 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 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 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 63-85 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 25082755-7 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 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 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 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 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 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 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 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 Bruton tyrosine kinase Homo sapiens 101-104 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 9-33 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 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 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 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 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 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 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 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 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 25042202-2 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 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 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 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 24697238-0 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 23782157-0 2013 Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. ibrutinib 19-28 Bruton tyrosine kinase Homo sapiens 10-13 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 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 23782158-0 2013 Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. ibrutinib 19-28 Bruton tyrosine kinase Homo sapiens 10-13 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 34732527-4 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 21-24 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 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 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 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 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 34912339-10 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 34912339-12 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 34214199-8 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 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 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 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 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 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 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 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 73-82 Bruton tyrosine kinase Homo sapiens 45-48 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 43-65 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 34099830-3 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 35437106-0 2022 Cardiotoxicity of BTK inhibitors: ibrutinib and beyond. ibrutinib 34-43 Bruton tyrosine kinase Homo sapiens 18-21 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 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 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 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 35179349-8 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 35448150-2 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 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 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 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 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 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 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 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 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 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 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 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 Bruton tyrosine kinase Homo sapiens 230-233 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 Bruton tyrosine kinase Homo sapiens 0-3 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 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 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 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 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 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 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 33216986-3 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 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 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 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 33730844-2 2021 The BTK inhibitor ibrutinib may be intolerable for some 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 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 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 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 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 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 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 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 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 Bruton tyrosine kinase Homo sapiens 57-60 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 Bruton tyrosine kinase Homo sapiens 125-128 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 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 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 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 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 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 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 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 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 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 32683672-14 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