PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
25982794-4	2015	We found that CBG caused the significant activation of ERK, JNK and p38 MAPK in U266 cells.	cinobufagin	14-17	mitogen-activated protein kinase 1	Homo sapiens	55-58
25982794-4	2015	We found that CBG caused the significant activation of ERK, JNK and p38 MAPK in U266 cells.	cinobufagin	14-17	mitogen-activated protein kinase 8	Homo sapiens	60-63
25982794-4	2015	We found that CBG caused the significant activation of ERK, JNK and p38 MAPK in U266 cells.	cinobufagin	14-17	mitogen-activated protein kinase 14	Homo sapiens	68-71
25982794-7	2015	Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly prevented CBG-induced ERK, JNK and p38 MAPK activation and apoptosis.	cinobufagin	82-85	X-linked Kx blood group	Homo sapiens	53-56
25982794-7	2015	Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly prevented CBG-induced ERK, JNK and p38 MAPK activation and apoptosis.	cinobufagin	82-85	mitogen-activated protein kinase 1	Homo sapiens	94-97
25982794-7	2015	Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly prevented CBG-induced ERK, JNK and p38 MAPK activation and apoptosis.	cinobufagin	82-85	mitogen-activated protein kinase 8	Homo sapiens	99-102
25982794-7	2015	Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly prevented CBG-induced ERK, JNK and p38 MAPK activation and apoptosis.	cinobufagin	82-85	mitogen-activated protein kinase 14	Homo sapiens	107-110
25982794-7	2015	Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly prevented CBG-induced ERK, JNK and p38 MAPK activation and apoptosis.	cinobufagin	82-85	mitogen-activated protein kinase 1	Homo sapiens	111-115
25982794-9	2015	Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells.	cinobufagin	71-74	mitogen-activated protein kinase 1	Homo sapiens	15-18
25982794-9	2015	Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells.	cinobufagin	71-74	mitogen-activated protein kinase 8	Homo sapiens	20-23
25982794-9	2015	Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells.	cinobufagin	71-74	caspase 3	Homo sapiens	159-168
25982794-9	2015	Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells.	cinobufagin	71-74	poly(ADP-ribose) polymerase 1	Homo sapiens	184-188
25982794-9	2015	Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells.	cinobufagin	147-150	mitogen-activated protein kinase 1	Homo sapiens	15-18
25982794-9	2015	Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells.	cinobufagin	147-150	mitogen-activated protein kinase 8	Homo sapiens	20-23
25982794-9	2015	Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells.	cinobufagin	147-150	mitogen-activated protein kinase 1	Homo sapiens	104-107
25982794-9	2015	Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells.	cinobufagin	147-150	caspase 3	Homo sapiens	159-168
25982794-9	2015	Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells.	cinobufagin	147-150	poly(ADP-ribose) polymerase 1	Homo sapiens	184-188
25982794-10	2015	Taken together, these findings suggest that CBG can act as a potent anticancer agent against MM and possibly exerts its effects through the ROS-mediated activation of ERK, JNK and p38 MAPK leading to the activation of caspase-3 in U266 cells.	cinobufagin	44-47	mitogen-activated protein kinase 1	Homo sapiens	167-170
25982794-10	2015	Taken together, these findings suggest that CBG can act as a potent anticancer agent against MM and possibly exerts its effects through the ROS-mediated activation of ERK, JNK and p38 MAPK leading to the activation of caspase-3 in U266 cells.	cinobufagin	44-47	mitogen-activated protein kinase 8	Homo sapiens	172-175
25982794-10	2015	Taken together, these findings suggest that CBG can act as a potent anticancer agent against MM and possibly exerts its effects through the ROS-mediated activation of ERK, JNK and p38 MAPK leading to the activation of caspase-3 in U266 cells.	cinobufagin	44-47	mitogen-activated protein kinase 14	Homo sapiens	180-183
25982794-10	2015	Taken together, these findings suggest that CBG can act as a potent anticancer agent against MM and possibly exerts its effects through the ROS-mediated activation of ERK, JNK and p38 MAPK leading to the activation of caspase-3 in U266 cells.	cinobufagin	44-47	caspase 3	Homo sapiens	218-227
24844018-4	2014	The Caspase-3 activity was measured by Caspase-3 activity assay kit at 48 hours after culture, which were treated with cinobufagin (20, 50, and 100 nmol/L), and simple U-2OS cells served as control group.	cinobufagin	119-130	caspase 3	Homo sapiens	4-13
26664411-8	2015	Finally, we found that CBG enhanced the secretion of IL-2 and IL-10 and increased the phagocytosis ability of macrophages.	cinobufagin	23-26	interleukin 2	Mus musculus	53-57
26664411-8	2015	Finally, we found that CBG enhanced the secretion of IL-2 and IL-10 and increased the phagocytosis ability of macrophages.	cinobufagin	23-26	interleukin 10	Mus musculus	62-67
24844018-12	2014	Compared with the control group, the expressions of cleaved Caspase-3, cleaved Caspase-9, and Bax were obviously up-regulated; the Bcl-2 expression was down-regulated; and the ratio of Bax/Bcl-2 was increased in different cinobufagin-treated groups (P < 0.05).	cinobufagin	222-233	BCL2 associated X, apoptosis regulator	Homo sapiens	185-188
23164673-8	2013	Furthermore, we validated the inhibition of GSK-3beta/NF-kappaB signaling following cinobufagin treatment.	cinobufagin	84-95	glycogen synthase kinase 3 beta	Homo sapiens	44-53
23164673-9	2013	Western blots showed a decrease in nuclear p65 protein expression after exposure to different concentrations of cinobufagin, while the phosphorylation of GSK-3beta was simultaneously increased.	cinobufagin	112-123	RELA proto-oncogene, NF-kB subunit	Homo sapiens	43-46
23164673-10	2013	Transduction with constitutively active forms of GSK-3beta could protect against the downregulation of p65 and upregulation of cleaved-PARP that are induced by cinobufagin treatment.	cinobufagin	160-171	glycogen synthase kinase 3 beta	Homo sapiens	49-58
23164673-10	2013	Transduction with constitutively active forms of GSK-3beta could protect against the downregulation of p65 and upregulation of cleaved-PARP that are induced by cinobufagin treatment.	cinobufagin	160-171	RELA proto-oncogene, NF-kB subunit	Homo sapiens	103-106
23164673-10	2013	Transduction with constitutively active forms of GSK-3beta could protect against the downregulation of p65 and upregulation of cleaved-PARP that are induced by cinobufagin treatment.	cinobufagin	160-171	collagen type XI alpha 2 chain	Homo sapiens	135-139
23164673-11	2013	However, combined treatment with cinobufagin and SB216367 resulted in a significant reduction in p65 and an increase in cleaved-PARP in U2OS cells.	cinobufagin	33-44	RELA proto-oncogene, NF-kB subunit	Homo sapiens	97-100
23164673-11	2013	However, combined treatment with cinobufagin and SB216367 resulted in a significant reduction in p65 and an increase in cleaved-PARP in U2OS cells.	cinobufagin	33-44	collagen type XI alpha 2 chain	Homo sapiens	128-132
23164673-13	2013	These studies are the first to reveal the involvement of the GSK-3beta/NF-kappaB pathway in cinobufagin-induced apoptosis.	cinobufagin	92-103	glycogen synthase kinase 3 beta	Homo sapiens	61-70
21215801-4	2011	Ouabain and cinobufagin significantly inhibited cell proliferation by attenuating the phosphorylation of extracellular regulated kinase (ERK) and down-regulating the expression of C-myc.	cinobufagin	12-23	mitogen-activated protein kinase 1	Homo sapiens	105-135
22178124-8	2012	It was found that bufalin, cinobufagin, and resibufogenin were novel CYP3A4 inducers.	cinobufagin	27-38	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	69-75
22178124-9	2012	Among them, bufalin and cinobufagin significantly promoted the CYP3A4 enzyme activity, mRNA and protein levels, with the maximal induction challenging or exceeding that of the induction by rifampicin, indicating that they might play a critical role in CYP3A4 enzyme-inducing effects of SBP.	cinobufagin	24-35	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	63-69
22178124-9	2012	Among them, bufalin and cinobufagin significantly promoted the CYP3A4 enzyme activity, mRNA and protein levels, with the maximal induction challenging or exceeding that of the induction by rifampicin, indicating that they might play a critical role in CYP3A4 enzyme-inducing effects of SBP.	cinobufagin	24-35	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	252-258
24187573-14	2013	Moreover, the expressions of beta -END, CRF, POMC, and mu -OR were significantly upregulated by cinobufagin.	cinobufagin	96-107	pro-opiomelanocortin-alpha	Mus musculus	45-49
24187573-17	2013	Cinobufagin significantly relieved cancer pain in mice and raised their pain threshold, mainly upregulating the expression levels of beta -END and mu -OR in the hind paw tumor and adjacent tissue.	cinobufagin	0-11	opioid receptor, mu 1	Mus musculus	133-153
21913902-0	2012	Inhibitory effect of bufalin and cinobufagin on steroidogenesis via the activation of ERK in human adrenocortical cells.	cinobufagin	33-44	mitogen-activated protein kinase 1	Homo sapiens	86-89
21913902-6	2012	KEY RESULTS: Bufalin and cinobufagin markedly inhibited basal, Ang II-, forskolin- or 8-Br-cAMP-stimulated aldosterone and cortisol secretion, and the conversions of corticosterone to aldosterone and deoxycortisol to cortisol.	cinobufagin	25-36	angiotensinogen	Homo sapiens	63-69
21913902-7	2012	Bufalin and cinobufagin also inhibited StAR protein expression and SF-1 binding to StAR gene promoter.	cinobufagin	12-23	steroidogenic acute regulatory protein	Homo sapiens	39-43
21913902-7	2012	Bufalin and cinobufagin also inhibited StAR protein expression and SF-1 binding to StAR gene promoter.	cinobufagin	12-23	splicing factor 1	Homo sapiens	67-71
21913902-7	2012	Bufalin and cinobufagin also inhibited StAR protein expression and SF-1 binding to StAR gene promoter.	cinobufagin	12-23	steroidogenic acute regulatory protein	Homo sapiens	83-87
21913902-9	2012	Furthermore, U0126 reversed the inhibitory effects of bufalin and cinobufagin on StAR protein expression and the binding of SF-1 to StAR gene promoter.	cinobufagin	66-77	steroidogenic acute regulatory protein	Homo sapiens	81-85
21913902-11	2012	CONCLUSIONS AND IMPLICATIONS: The inhibitory effects of bufalin and cinobufagin on steroidogenesis of aldosterone and cortisol were associated with inhibition of aldosterone synthase and 11beta-hydroxylase, as well as the suppression of StAR protein expression and SF-1 binding to StAR promoter via the phosphorylation of ERK1/2 in H295 cells.	cinobufagin	68-79	steroidogenic acute regulatory protein	Homo sapiens	237-241
21913902-11	2012	CONCLUSIONS AND IMPLICATIONS: The inhibitory effects of bufalin and cinobufagin on steroidogenesis of aldosterone and cortisol were associated with inhibition of aldosterone synthase and 11beta-hydroxylase, as well as the suppression of StAR protein expression and SF-1 binding to StAR promoter via the phosphorylation of ERK1/2 in H295 cells.	cinobufagin	68-79	splicing factor 1	Homo sapiens	265-269
21913902-11	2012	CONCLUSIONS AND IMPLICATIONS: The inhibitory effects of bufalin and cinobufagin on steroidogenesis of aldosterone and cortisol were associated with inhibition of aldosterone synthase and 11beta-hydroxylase, as well as the suppression of StAR protein expression and SF-1 binding to StAR promoter via the phosphorylation of ERK1/2 in H295 cells.	cinobufagin	68-79	steroidogenic acute regulatory protein	Homo sapiens	281-285
21913902-11	2012	CONCLUSIONS AND IMPLICATIONS: The inhibitory effects of bufalin and cinobufagin on steroidogenesis of aldosterone and cortisol were associated with inhibition of aldosterone synthase and 11beta-hydroxylase, as well as the suppression of StAR protein expression and SF-1 binding to StAR promoter via the phosphorylation of ERK1/2 in H295 cells.	cinobufagin	68-79	mitogen-activated protein kinase 3	Homo sapiens	322-328
21215801-4	2011	Ouabain and cinobufagin significantly inhibited cell proliferation by attenuating the phosphorylation of extracellular regulated kinase (ERK) and down-regulating the expression of C-myc.	cinobufagin	12-23	mitogen-activated protein kinase 1	Homo sapiens	137-140
21215801-4	2011	Ouabain and cinobufagin significantly inhibited cell proliferation by attenuating the phosphorylation of extracellular regulated kinase (ERK) and down-regulating the expression of C-myc.	cinobufagin	12-23	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	180-185
21215801-6	2011	Overexpression of ERK reversed the antiproliferation effect of ouabain or cinobufagin in HepG2 and SMMC-7721 cells.	cinobufagin	74-85	mitogen-activated protein kinase 1	Homo sapiens	18-21
21288283-7	2011	In addition, caspase activation during bufalin- and cinobufagin-induced apoptosis was further confirmed by caspase-3 inhibitor Z-DEVD-FMK, caspase-8 inhibitor Z-IETD-FMK, caspase-9 inhibitor Z-LEHD-FMK and caspase-10 inhibitor Z-AEVD-FMK.	cinobufagin	52-63	caspase 3	Homo sapiens	107-116
21288283-8	2011	The results showed that bufalin- and cinobufagin-induced apoptosis was blocked by these inhibitors and particularly by caspase-10 inhibitor.	cinobufagin	37-48	caspase 10	Homo sapiens	119-129
21288283-7	2011	In addition, caspase activation during bufalin- and cinobufagin-induced apoptosis was further confirmed by caspase-3 inhibitor Z-DEVD-FMK, caspase-8 inhibitor Z-IETD-FMK, caspase-9 inhibitor Z-LEHD-FMK and caspase-10 inhibitor Z-AEVD-FMK.	cinobufagin	52-63	caspase 8	Homo sapiens	139-148
21288283-7	2011	In addition, caspase activation during bufalin- and cinobufagin-induced apoptosis was further confirmed by caspase-3 inhibitor Z-DEVD-FMK, caspase-8 inhibitor Z-IETD-FMK, caspase-9 inhibitor Z-LEHD-FMK and caspase-10 inhibitor Z-AEVD-FMK.	cinobufagin	52-63	caspase 9	Homo sapiens	171-180
21288283-7	2011	In addition, caspase activation during bufalin- and cinobufagin-induced apoptosis was further confirmed by caspase-3 inhibitor Z-DEVD-FMK, caspase-8 inhibitor Z-IETD-FMK, caspase-9 inhibitor Z-LEHD-FMK and caspase-10 inhibitor Z-AEVD-FMK.	cinobufagin	52-63	caspase 10	Homo sapiens	206-216
15494417-4	2005	At a concentration of 1 microM, ouabain and other tested cardenolides, as well as bufadienolides such as bufalin, cinobufagin, cinobufotalin, and telobufotoxin, led to approximately 10-fold inhibition of the Na(+),K(+) pump, a 2-3-fold decrease in staining with dimethylthiazol-diphenyltetrazolium (MTT), and massive death indicated by detachment of approximately 80% of cells and caspase-3 activation.	cinobufagin	114-125	caspase 3	Canis lupus familiaris	381-390
21472305-13	2010	Western blot analysis showed that cinobufagin up-regulated Bax expression and down-regulated Bcl-2 expression.	cinobufagin	34-45	BCL2 associated X, apoptosis regulator	Homo sapiens	59-62
21472305-13	2010	Western blot analysis showed that cinobufagin up-regulated Bax expression and down-regulated Bcl-2 expression.	cinobufagin	34-45	BCL2 apoptosis regulator	Homo sapiens	93-98
20118004-1	2010	OBJECTIVE: To investigate the effect of cinobufagin on nuclear factor-kappaB (NF-kappaB) pathway of liver cancer cell line HepG2.	cinobufagin	40-51	nuclear factor kappa B subunit 1	Homo sapiens	78-87
20118004-5	2010	The results of Western blotting showed that cinobufagin significantly suppressed the protein expression of NF-kappaB p65.	cinobufagin	44-55	nuclear factor kappa B subunit 1	Homo sapiens	107-116
20118004-5	2010	The results of Western blotting showed that cinobufagin significantly suppressed the protein expression of NF-kappaB p65.	cinobufagin	44-55	RELA proto-oncogene, NF-kB subunit	Homo sapiens	117-120
20118004-6	2010	The transcription level of ICAM-1 was reduced by different doses of cinobufagin.	cinobufagin	68-79	intercellular adhesion molecule 1	Homo sapiens	27-33
20118004-7	2010	CONCLUSION: The anti-cancer effect of cinobufagin may be related to its activity in inhibiting the activation of NF-kappaB pathway.	cinobufagin	38-49	nuclear factor kappa B subunit 1	Homo sapiens	113-122
20073224-0	2009	[Effect of cinobufagin on the expressions of bcl-2 mRNA and bax mRNA and the proliferation of lens epithelial cells].	cinobufagin	11-22	BCL-2	Oryctolagus cuniculus	45-50
20073224-0	2009	[Effect of cinobufagin on the expressions of bcl-2 mRNA and bax mRNA and the proliferation of lens epithelial cells].	cinobufagin	11-22	apoptosis regulator BAX	Oryctolagus cuniculus	60-63
19037992-13	2008	These results suggest that bufalin and cinobufagin suppress cell proliferation and cause apoptosis in prostate cancer cells via a sequence of apoptotic modulators, including Bax, cytochrome c, and caspases.	cinobufagin	39-50	BCL2 associated X, apoptosis regulator	Homo sapiens	174-177
19037992-13	2008	These results suggest that bufalin and cinobufagin suppress cell proliferation and cause apoptosis in prostate cancer cells via a sequence of apoptotic modulators, including Bax, cytochrome c, and caspases.	cinobufagin	39-50	cytochrome c, somatic	Homo sapiens	179-191
19037992-13	2008	These results suggest that bufalin and cinobufagin suppress cell proliferation and cause apoptosis in prostate cancer cells via a sequence of apoptotic modulators, including Bax, cytochrome c, and caspases.	cinobufagin	39-50	caspase 8	Homo sapiens	197-205
35114328-0	2022	Chemically synthesized cinobufagin suppresses nasopharyngeal carcinoma metastasis by inducing ENKUR to stabilize p53 expression.	cinobufagin	23-34	enkurin, TRPC channel interacting protein	Homo sapiens	94-99
12497584-2	2003	This study was to evaluate bufalin and cinobufagin effects on the proliferation of prostate cancer cell lines named LNCaP, DU145, and PC3.	cinobufagin	39-50	chromobox 8	Homo sapiens	134-137
12497584-10	2003	Bufalin or cinobufagin increased [Ca(2+)](i) and apoptosis in cancer cells after a 24-hr culture as well as caspase 3 activities in DU145 and PC3 cells and caspase 9 activities in LNCaP cells.	cinobufagin	11-22	caspase 3	Homo sapiens	108-117
12497584-10	2003	Bufalin or cinobufagin increased [Ca(2+)](i) and apoptosis in cancer cells after a 24-hr culture as well as caspase 3 activities in DU145 and PC3 cells and caspase 9 activities in LNCaP cells.	cinobufagin	11-22	chromobox 8	Homo sapiens	142-145
12497584-10	2003	Bufalin or cinobufagin increased [Ca(2+)](i) and apoptosis in cancer cells after a 24-hr culture as well as caspase 3 activities in DU145 and PC3 cells and caspase 9 activities in LNCaP cells.	cinobufagin	11-22	caspase 9	Homo sapiens	156-165
34740818-3	2021	In a target identification assay of anti-cancer compound using a modified DrugTargetSeqR strategy, mutation of TOP3B was detected in cancer cells acquired resistance to cinobufagin (CBG), a key compound of Huachansu that has been approved for cancer therapy in China.	cinobufagin	169-180	DNA topoisomerase III beta	Homo sapiens	111-116
34740818-3	2021	In a target identification assay of anti-cancer compound using a modified DrugTargetSeqR strategy, mutation of TOP3B was detected in cancer cells acquired resistance to cinobufagin (CBG), a key compound of Huachansu that has been approved for cancer therapy in China.	cinobufagin	182-185	DNA topoisomerase III beta	Homo sapiens	111-116
34740818-4	2021	We demonstrated that CBG directly engaged with TOP3beta, and promoted TOP3beta depletion in wildtype but not mutant cancer cells.	cinobufagin	21-24	DNA topoisomerase III alpha	Homo sapiens	47-55
34740818-4	2021	We demonstrated that CBG directly engaged with TOP3beta, and promoted TOP3beta depletion in wildtype but not mutant cancer cells.	cinobufagin	21-24	DNA topoisomerase III alpha	Homo sapiens	70-78
34740818-6	2021	We also demonstrated that CBG induced formation of stress granule, RNA-loop and asymmetric DNA damages in cancer cells, and all these phenotypes were significantly attenuated in TOP3B knockout cells.	cinobufagin	26-29	DNA topoisomerase III beta	Homo sapiens	178-183
34740818-7	2021	Of note, examination of a panel of cancer cell lines revealed associations among cell growth inhibition and induction of DNA damage as well as TOP3B depletion upon CBG treatment.	cinobufagin	164-167	DNA topoisomerase III beta	Homo sapiens	143-148
34740818-8	2021	Our findings not only highlighted TOP3beta as a promising therapeutic target of cancer, but also identified CBG as a lead chemical inhibitor of TOP3beta for cancer therapy.	cinobufagin	108-111	DNA topoisomerase III alpha	Homo sapiens	34-42
34740818-8	2021	Our findings not only highlighted TOP3beta as a promising therapeutic target of cancer, but also identified CBG as a lead chemical inhibitor of TOP3beta for cancer therapy.	cinobufagin	108-111	DNA topoisomerase III alpha	Homo sapiens	144-152
34925034-0	2021	Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion.	cinobufagin	0-11	epidermal growth factor receptor	Homo sapiens	65-69
34925034-0	2021	Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion.	cinobufagin	0-11	phosphatase and tensin homolog	Homo sapiens	88-92
34925034-4	2021	We screened a chemical library containing over 600 individual compounds purified from Traditional Chinese Medicine against GBM cells with EGFR amplification and found that cinobufagin, the major active ingredient of Chansu, inhibited the proliferation of EGFR amplified GBM cells and PTEN deficiency enhanced its anti-proliferation effects.	cinobufagin	172-183	epidermal growth factor receptor	Homo sapiens	255-259
34925034-7	2021	Cinobufagin blocked EGFR phosphorylation and its downstream signaling, which additionally induced apoptosis and cytotoxicity in EGFR amplified cancer cells.	cinobufagin	0-11	epidermal growth factor receptor	Homo sapiens	20-24
34925034-7	2021	Cinobufagin blocked EGFR phosphorylation and its downstream signaling, which additionally induced apoptosis and cytotoxicity in EGFR amplified cancer cells.	cinobufagin	0-11	epidermal growth factor receptor	Homo sapiens	128-132
34925034-8	2021	In vivo, cinobufagin blocked EGFR signaling, inhibited cell proliferation, and elicited apoptosis, thereby suppressing tumor growth in both subcutaneous and intracranial U87MG-EGFR xenograft mouse models and increasing the median survival of nude mice bearing intracranial U87MG-EGFR tumors.	cinobufagin	9-20	epidermal growth factor receptor	Mus musculus	29-33
34925034-8	2021	In vivo, cinobufagin blocked EGFR signaling, inhibited cell proliferation, and elicited apoptosis, thereby suppressing tumor growth in both subcutaneous and intracranial U87MG-EGFR xenograft mouse models and increasing the median survival of nude mice bearing intracranial U87MG-EGFR tumors.	cinobufagin	9-20	epidermal growth factor receptor	Mus musculus	176-180
34925034-8	2021	In vivo, cinobufagin blocked EGFR signaling, inhibited cell proliferation, and elicited apoptosis, thereby suppressing tumor growth in both subcutaneous and intracranial U87MG-EGFR xenograft mouse models and increasing the median survival of nude mice bearing intracranial U87MG-EGFR tumors.	cinobufagin	9-20	epidermal growth factor receptor	Mus musculus	279-283
34925034-9	2021	Cinobufagin is a potential therapeutic agent for treating malignant glioma and other human cancers expressing EGFR.	cinobufagin	0-11	epidermal growth factor receptor	Homo sapiens	110-114
34619160-0	2021	A network pharmacology approach to investigate the anticancer mechanism of cinobufagin against hepatocellular carcinoma via downregulation of EGFR-CDK2 signaling.	cinobufagin	75-86	epidermal growth factor receptor	Homo sapiens	142-146
34619160-0	2021	A network pharmacology approach to investigate the anticancer mechanism of cinobufagin against hepatocellular carcinoma via downregulation of EGFR-CDK2 signaling.	cinobufagin	75-86	cyclin dependent kinase 2	Homo sapiens	147-151
34619160-5	2021	Inhibition of EGFR or CDK2 expression could not only suppress the growth of tumor cells but also enhance the inhibitory effects of cinobufagin on the proliferative potential of human hepatoma cells.	cinobufagin	131-142	epidermal growth factor receptor	Homo sapiens	14-18
34619160-5	2021	Inhibition of EGFR or CDK2 expression could not only suppress the growth of tumor cells but also enhance the inhibitory effects of cinobufagin on the proliferative potential of human hepatoma cells.	cinobufagin	131-142	cyclin dependent kinase 2	Homo sapiens	22-26
34619160-7	2021	Furthermore, EGFR inhibitor gefitinib or CDK2 inhibitor CVT-313 synergistically enhances anticancer effects of cinobufagin in human hepatoma cells.	cinobufagin	111-122	epidermal growth factor receptor	Homo sapiens	13-17
34619160-7	2021	Furthermore, EGFR inhibitor gefitinib or CDK2 inhibitor CVT-313 synergistically enhances anticancer effects of cinobufagin in human hepatoma cells.	cinobufagin	111-122	cyclin dependent kinase 2	Homo sapiens	41-45
34619160-8	2021	Taken together, these findings indicate that cinobufagin may exert antitumor effects by suppressing EGFR-CDK2 signaling, and our study suggests that cinobufagin may be a novel, promising anticancer agent for the treatment of HCC.	cinobufagin	45-56	epidermal growth factor receptor	Homo sapiens	100-104
34619160-8	2021	Taken together, these findings indicate that cinobufagin may exert antitumor effects by suppressing EGFR-CDK2 signaling, and our study suggests that cinobufagin may be a novel, promising anticancer agent for the treatment of HCC.	cinobufagin	45-56	cyclin dependent kinase 2	Homo sapiens	105-109
35427566-6	2022	We demonstrate that cinobufagin suppresses TYMS expression via proteasome-dependent degradation in human hepatoma cells, moreover, depletion of TYMS restrains the proliferation and colony formation of tumor cells, and the results of western blotting and immunofluorescence assay indicate DNA damage is induced in tumor cells transfected with TYMS-targeting siRNA (siTYMS), additionally, knockdown of TYMS enhances the inhibitory effect of cinobufagin on the proliferative potential of HepG2 and SK-HEP-1 cells.	cinobufagin	20-31	thymidylate synthetase	Homo sapiens	43-47
35427566-6	2022	We demonstrate that cinobufagin suppresses TYMS expression via proteasome-dependent degradation in human hepatoma cells, moreover, depletion of TYMS restrains the proliferation and colony formation of tumor cells, and the results of western blotting and immunofluorescence assay indicate DNA damage is induced in tumor cells transfected with TYMS-targeting siRNA (siTYMS), additionally, knockdown of TYMS enhances the inhibitory effect of cinobufagin on the proliferative potential of HepG2 and SK-HEP-1 cells.	cinobufagin	20-31	thymidylate synthetase	Homo sapiens	144-148
35427566-6	2022	We demonstrate that cinobufagin suppresses TYMS expression via proteasome-dependent degradation in human hepatoma cells, moreover, depletion of TYMS restrains the proliferation and colony formation of tumor cells, and the results of western blotting and immunofluorescence assay indicate DNA damage is induced in tumor cells transfected with TYMS-targeting siRNA (siTYMS), additionally, knockdown of TYMS enhances the inhibitory effect of cinobufagin on the proliferative potential of HepG2 and SK-HEP-1 cells.	cinobufagin	20-31	thymidylate synthetase	Homo sapiens	342-346
35427566-6	2022	We demonstrate that cinobufagin suppresses TYMS expression via proteasome-dependent degradation in human hepatoma cells, moreover, depletion of TYMS restrains the proliferation and colony formation of tumor cells, and the results of western blotting and immunofluorescence assay indicate DNA damage is induced in tumor cells transfected with TYMS-targeting siRNA (siTYMS), additionally, knockdown of TYMS enhances the inhibitory effect of cinobufagin on the proliferative potential of HepG2 and SK-HEP-1 cells.	cinobufagin	20-31	thymidylate synthetase	Homo sapiens	400-404
35427566-6	2022	We demonstrate that cinobufagin suppresses TYMS expression via proteasome-dependent degradation in human hepatoma cells, moreover, depletion of TYMS restrains the proliferation and colony formation of tumor cells, and the results of western blotting and immunofluorescence assay indicate DNA damage is induced in tumor cells transfected with TYMS-targeting siRNA (siTYMS), additionally, knockdown of TYMS enhances the inhibitory effect of cinobufagin on the proliferative potential of HepG2 and SK-HEP-1 cells.	cinobufagin	439-450	thymidylate synthetase	Homo sapiens	144-148
35427566-8	2022	Collectively, cinobufagin exerts good anti-hepatoma activity through inhibition of growth and induction of DNA damage by promoting the degradation of TYMS.	cinobufagin	14-25	thymidylate synthetase	Homo sapiens	150-154
21534035-3	2011	CBG also significantly increased CD4(+)CD8(+) double-positive T-cell populations and the percentage of S-phase cells of splenic lymphocytes.	cinobufagin	0-3	CD4 molecule	Homo sapiens	33-36
21534035-3	2011	CBG also significantly increased CD4(+)CD8(+) double-positive T-cell populations and the percentage of S-phase cells of splenic lymphocytes.	cinobufagin	0-3	CD8a molecule	Homo sapiens	39-42
21534035-4	2011	The levels of several Th1 cytokines, including interferon-gamma and tumor necrosis factor-alpha, are significantly increased after CBG treatment, whereas the levels of the Th2 cytokine interleukin-4 and interleukin-10 are significantly decreased.	cinobufagin	131-134	negative elongation factor complex member C/D	Homo sapiens	22-25
21534035-4	2011	The levels of several Th1 cytokines, including interferon-gamma and tumor necrosis factor-alpha, are significantly increased after CBG treatment, whereas the levels of the Th2 cytokine interleukin-4 and interleukin-10 are significantly decreased.	cinobufagin	131-134	interferon gamma	Homo sapiens	47-95
21534035-4	2011	The levels of several Th1 cytokines, including interferon-gamma and tumor necrosis factor-alpha, are significantly increased after CBG treatment, whereas the levels of the Th2 cytokine interleukin-4 and interleukin-10 are significantly decreased.	cinobufagin	131-134	interleukin 4	Homo sapiens	185-198
21534035-4	2011	The levels of several Th1 cytokines, including interferon-gamma and tumor necrosis factor-alpha, are significantly increased after CBG treatment, whereas the levels of the Th2 cytokine interleukin-4 and interleukin-10 are significantly decreased.	cinobufagin	131-134	interleukin 10	Homo sapiens	203-217
34769467-0	2021	Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1.	cinobufagin	0-11	anoctamin 1	Homo sapiens	103-107
34769467-5	2021	ANO1 protein levels were significantly reduced by cinobufagin in a dose-dependent manner with an IC50 value of ~26 nM.	cinobufagin	50-61	anoctamin 1	Homo sapiens	0-4
34769467-6	2021	Unlike previous ANO1 inhibitors, short-term (<=10 min) exposure to cinobufagin did not alter ANO1 chloride channel activity and ANO1-dependent intestinal smooth muscle contraction, whereas long-term (24 h) exposure to cinobufagin significantly reduced phosphorylation of STAT3 and mRNA expression of ANO1 in CAL-27 cells.	cinobufagin	67-78	anoctamin 1	Homo sapiens	300-304
34769467-6	2021	Unlike previous ANO1 inhibitors, short-term (<=10 min) exposure to cinobufagin did not alter ANO1 chloride channel activity and ANO1-dependent intestinal smooth muscle contraction, whereas long-term (24 h) exposure to cinobufagin significantly reduced phosphorylation of STAT3 and mRNA expression of ANO1 in CAL-27 cells.	cinobufagin	218-229	signal transducer and activator of transcription 3	Homo sapiens	271-276
34769467-6	2021	Unlike previous ANO1 inhibitors, short-term (<=10 min) exposure to cinobufagin did not alter ANO1 chloride channel activity and ANO1-dependent intestinal smooth muscle contraction, whereas long-term (24 h) exposure to cinobufagin significantly reduced phosphorylation of STAT3 and mRNA expression of ANO1 in CAL-27 cells.	cinobufagin	218-229	anoctamin 1	Homo sapiens	300-304
34769467-8	2021	In addition, cinobufagin significantly reduced cell migration and induced caspase-3 activation and PARP cleavage in CAL-27 cells.	cinobufagin	13-24	caspase 3	Homo sapiens	74-83
34769467-8	2021	In addition, cinobufagin significantly reduced cell migration and induced caspase-3 activation and PARP cleavage in CAL-27 cells.	cinobufagin	13-24	poly(ADP-ribose) polymerase 1	Homo sapiens	99-103
34769467-9	2021	These results suggest that downregulation of ANO1 by cinobufagin is a potential mechanism for the anticancer effect of cinobufagin in OSCC.	cinobufagin	53-64	anoctamin 1	Homo sapiens	45-49
34769467-9	2021	These results suggest that downregulation of ANO1 by cinobufagin is a potential mechanism for the anticancer effect of cinobufagin in OSCC.	cinobufagin	119-130	anoctamin 1	Homo sapiens	45-49
34737550-0	2021	Cinobufagin Suppresses the Characteristics of Osteosarcoma Cancer Cells by Inhibiting the IL-6-OPN-STAT3 Pathway (Retraction).	cinobufagin	0-11	interleukin 6	Homo sapiens	90-94
34737550-0	2021	Cinobufagin Suppresses the Characteristics of Osteosarcoma Cancer Cells by Inhibiting the IL-6-OPN-STAT3 Pathway (Retraction).	cinobufagin	0-11	secreted phosphoprotein 1	Homo sapiens	95-98
34737550-0	2021	Cinobufagin Suppresses the Characteristics of Osteosarcoma Cancer Cells by Inhibiting the IL-6-OPN-STAT3 Pathway (Retraction).	cinobufagin	0-11	signal transducer and activator of transcription 3	Homo sapiens	99-104
35176466-0	2022	Cinobufagin induces FOXO1-regulated apoptosis, proliferation, migration, and invasion by inhibiting G9a in non-small-cell lung cancer A549 cells.	cinobufagin	0-11	forkhead box O1	Homo sapiens	20-25
35176466-0	2022	Cinobufagin induces FOXO1-regulated apoptosis, proliferation, migration, and invasion by inhibiting G9a in non-small-cell lung cancer A549 cells.	cinobufagin	0-11	euchromatic histone lysine methyltransferase 2	Homo sapiens	100-103
35176466-12	2022	CONCLUSION: Our study provides the first evidence that cinobufagin suppresses the malignant biological behaviours of NSCLC cells in vivo and in vitro and suggests that mechanistically, this effect may be achieved by inhibiting the expression of the histone methyltransferase G9a and activating the tumour suppressor gene FOXO1.	cinobufagin	55-66	forkhead box O1	Homo sapiens	321-326
35114328-0	2022	Chemically synthesized cinobufagin suppresses nasopharyngeal carcinoma metastasis by inducing ENKUR to stabilize p53 expression.	cinobufagin	23-34	tumor protein p53	Homo sapiens	113-116
33520369-0	2021	Cinobufagin suppresses colorectal cancer growth via STAT3 pathway inhibition.	cinobufagin	0-11	signal transducer and activator of transcription 3	Homo sapiens	52-57
33520369-5	2021	Mechanistically, cinobufagin simultaneously suppressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and blocked the interleukin-6 (IL6)-induced nuclear translocation of STAT3.	cinobufagin	17-28	signal transducer and activator of transcription 3	Homo sapiens	78-128
33520369-5	2021	Mechanistically, cinobufagin simultaneously suppressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and blocked the interleukin-6 (IL6)-induced nuclear translocation of STAT3.	cinobufagin	17-28	signal transducer and activator of transcription 3	Homo sapiens	130-135
33520369-5	2021	Mechanistically, cinobufagin simultaneously suppressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and blocked the interleukin-6 (IL6)-induced nuclear translocation of STAT3.	cinobufagin	17-28	interleukin 6	Homo sapiens	153-166
33520369-5	2021	Mechanistically, cinobufagin simultaneously suppressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and blocked the interleukin-6 (IL6)-induced nuclear translocation of STAT3.	cinobufagin	17-28	interleukin 6	Homo sapiens	168-171
33520369-5	2021	Mechanistically, cinobufagin simultaneously suppressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and blocked the interleukin-6 (IL6)-induced nuclear translocation of STAT3.	cinobufagin	17-28	signal transducer and activator of transcription 3	Homo sapiens	206-211
33520369-7	2021	Furthermore, cinobufagin suppressed EMT in CRC by inhibiting the STAT3 pathway.	cinobufagin	13-24	signal transducer and activator of transcription 3	Homo sapiens	65-70
33520369-9	2021	Cinobufagin may be used clinically as a novel STAT3 inhibitor for CRC adjuvant therapy.	cinobufagin	0-11	signal transducer and activator of transcription 3	Homo sapiens	46-51
31572194-6	2019	We investigated the hypothesis that cinobufagin plays an inhibitory role on TGF-beta1 signaling using a luciferase-reporter assay.	cinobufagin	36-47	transforming growth factor, beta 1	Mus musculus	76-85
32933177-8	2020	In addition, ectopic LEF1 expression is sufficient to attenuate cinobufagin-induced apoptosis and cell growth retardation in melanoma cells.	cinobufagin	64-75	lymphoid enhancer binding factor 1	Homo sapiens	21-25
32933177-9	2020	Thus, we suggest that cinobufagin is a potential anti-melanoma drug that suppresses tumor-promoting Wnt/beta-catenin signaling via LEF1 inhibition.	cinobufagin	22-33	catenin beta 1	Homo sapiens	104-116
32933177-9	2020	Thus, we suggest that cinobufagin is a potential anti-melanoma drug that suppresses tumor-promoting Wnt/beta-catenin signaling via LEF1 inhibition.	cinobufagin	22-33	lymphoid enhancer binding factor 1	Homo sapiens	131-135
32113469-0	2020	The spinal microglial IL-10/beta-endorphin pathway accounts for cinobufagin-induced mechanical antiallodynia in bone cancer pain following activation of alpha7-nicotinic acetylcholine receptors.	cinobufagin	64-75	interleukin 10	Rattus norvegicus	22-27
32113469-7	2020	Intrathecal cinobufagin also stimulated the gene and protein expression of IL-10 and beta-endorphin (but not dynorphin A) in the spinal cords of bone cancer pain rats.	cinobufagin	12-23	interleukin 10	Rattus norvegicus	75-80
32113469-8	2020	In addition, treatment with cinobufagin in cultured primary spinal microglia but not astrocytes or neurons stimulated the mRNA and protein expression of IL-10 and beta-endorphin, which was prevented by the pretreatment with the IL-10 antibody but not beta-endorphin antiserum.	cinobufagin	28-39	interleukin 10	Rattus norvegicus	153-158
32113469-8	2020	In addition, treatment with cinobufagin in cultured primary spinal microglia but not astrocytes or neurons stimulated the mRNA and protein expression of IL-10 and beta-endorphin, which was prevented by the pretreatment with the IL-10 antibody but not beta-endorphin antiserum.	cinobufagin	28-39	interleukin 10	Rattus norvegicus	228-233
32113469-9	2020	Furthermore, spinal cinobufagin-induced mechanical antiallodynia was inhibited by the pretreatment with intrathecal injection of the microglial inhibitor minocycline, IL-10 antibody, beta-endorphin antiserum and specific mu-opioid receptor antagonist CTAP.	cinobufagin	20-31	interleukin 10	Rattus norvegicus	167-172
32113469-10	2020	Lastly, cinobufagin- and the specific alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) agonist PHA-543613-induced microglial gene expression of IL-10/beta-endorphin and mechanical antiallodynia in bone cancer pain were blocked by the pretreatment with the specific alpha7-nAChR antagonist methyllycaconitine.	cinobufagin	8-19	interleukin 10	Rattus norvegicus	151-156
32113469-11	2020	CONCLUSIONS: Our results illustrate that cinobufagin produces mechanical antiallodynia in bone cancer pain through spinal microglial expression of IL-10 and subsequent beta-endorphin following activation of alpha7-nAChRs.	cinobufagin	41-52	interleukin 10	Rattus norvegicus	147-152
32349518-0	2020	Cinobufagin Triggers Defects in Spindle Formation and Cap-Dependent Translation in Liver Cancer Cells by Inhibiting the AURKA-mTOR-eIF4E Axis.	cinobufagin	0-11	aurora kinase A	Homo sapiens	120-125
32349518-0	2020	Cinobufagin Triggers Defects in Spindle Formation and Cap-Dependent Translation in Liver Cancer Cells by Inhibiting the AURKA-mTOR-eIF4E Axis.	cinobufagin	0-11	mechanistic target of rapamycin kinase	Homo sapiens	126-130
32349518-0	2020	Cinobufagin Triggers Defects in Spindle Formation and Cap-Dependent Translation in Liver Cancer Cells by Inhibiting the AURKA-mTOR-eIF4E Axis.	cinobufagin	0-11	eukaryotic translation initiation factor 4E	Homo sapiens	131-136
32349518-2	2020	The purpose of the present study was to clarify the underlying mechanism of the anticancer effects of cinobufagin using overexpression or inhibition of aurora kinase A (AURKA) signaling.	cinobufagin	102-113	aurora kinase A	Homo sapiens	152-167
32349518-4	2020	After treatment with cinobufagin, we successfully screened 202, 249, and 335 changing expression proteins in Huh-7 cells under normal, overexpression, and inhibition of AURKA using tandem mass tags (TMT)-labeled quantitative proteomics coupled to 2D liquid chromatography-tandem mass spectrometry (LC-MS/MS).	cinobufagin	21-32	aurora kinase A	Homo sapiens	169-174
32349518-7	2020	Our results suggested that cinobufagin performed an antitumor effects in liver cancer cells by inhibiting the AURKA-mTOR-eIF4E axis.	cinobufagin	27-38	aurora kinase A	Homo sapiens	110-115
32349518-7	2020	Our results suggested that cinobufagin performed an antitumor effects in liver cancer cells by inhibiting the AURKA-mTOR-eIF4E axis.	cinobufagin	27-38	mechanistic target of rapamycin kinase	Homo sapiens	116-120
32349518-7	2020	Our results suggested that cinobufagin performed an antitumor effects in liver cancer cells by inhibiting the AURKA-mTOR-eIF4E axis.	cinobufagin	27-38	eukaryotic translation initiation factor 4E	Homo sapiens	121-126
32933177-0	2020	Cinobufagin Suppresses Melanoma Cell Growth by Inhibiting LEF1.	cinobufagin	0-11	lymphoid enhancer binding factor 1	Homo sapiens	58-62
32933177-5	2020	A luciferase assay-based high throughput screening (HTS) with a natural compound library showed that cinobufagin suppressed beta-catenin/TCF4 transcriptional activity by inhibiting LEF1 expression.	cinobufagin	101-112	catenin beta 1	Homo sapiens	124-136
32933177-5	2020	A luciferase assay-based high throughput screening (HTS) with a natural compound library showed that cinobufagin suppressed beta-catenin/TCF4 transcriptional activity by inhibiting LEF1 expression.	cinobufagin	101-112	transcription factor 4	Homo sapiens	137-141
32933177-5	2020	A luciferase assay-based high throughput screening (HTS) with a natural compound library showed that cinobufagin suppressed beta-catenin/TCF4 transcriptional activity by inhibiting LEF1 expression.	cinobufagin	101-112	lymphoid enhancer binding factor 1	Homo sapiens	181-185
32933177-7	2020	Cinobufagin sensitively attenuates cell viability and induces apoptosis in LEF1 expressing melanoma cells compared to LEF1-low expressing lung cancer cells.	cinobufagin	0-11	lymphoid enhancer binding factor 1	Homo sapiens	75-79
31918288-3	2020	In this study, we found that cinobufagin significantly inhibits the proliferation of nasopharyngeal carcinoma HK-1 cells.	cinobufagin	29-40	hexokinase 1	Homo sapiens	110-114
31918288-5	2020	Furthermore, we found that cinobufagin significantly increases ROS levels and decreases the mitochondrial membrane potential in HK-1 cells.	cinobufagin	27-38	hexokinase 1	Homo sapiens	128-132
31918288-6	2020	Collectively, these data imply that cinobufagin induces cell cycle arrest at the S phase and induces apoptosis through increasing ROS levels, thereby inhibiting cell proliferation in HK-1 cells.	cinobufagin	36-47	hexokinase 1	Homo sapiens	183-187
31824138-0	2019	Cinobufagin Suppresses The Characteristics Of Osteosarcoma Cancer Cells By Inhibiting The IL-6-OPN-STAT3 Pathway.	cinobufagin	0-11	interleukin 6	Homo sapiens	90-94
31824138-0	2019	Cinobufagin Suppresses The Characteristics Of Osteosarcoma Cancer Cells By Inhibiting The IL-6-OPN-STAT3 Pathway.	cinobufagin	0-11	secreted phosphoprotein 1	Homo sapiens	95-98
31824138-0	2019	Cinobufagin Suppresses The Characteristics Of Osteosarcoma Cancer Cells By Inhibiting The IL-6-OPN-STAT3 Pathway.	cinobufagin	0-11	signal transducer and activator of transcription 3	Homo sapiens	99-104
31824138-12	2019	Moreover, cinobufagin induced apoptosis, increased the width of wounds, reduced invasive osteosarcoma spheroids/parent cell numbers and reduced EMT phenotype and OPN levels in U2OS/MG-63 spheroids as well as U2OS/MG-63 parent cells lines.	cinobufagin	10-21	secreted phosphoprotein 1	Homo sapiens	162-165
31824138-14	2019	In addition, cinobufagin ameliorated the proportion of CD133-positive cells, the size of spheroids and Nanog, Sox-2 and Oct3/4 protein levels.	cinobufagin	13-24	prominin 1	Homo sapiens	55-60
31824138-14	2019	In addition, cinobufagin ameliorated the proportion of CD133-positive cells, the size of spheroids and Nanog, Sox-2 and Oct3/4 protein levels.	cinobufagin	13-24	Nanog homeobox	Homo sapiens	103-108
31824138-14	2019	In addition, cinobufagin ameliorated the proportion of CD133-positive cells, the size of spheroids and Nanog, Sox-2 and Oct3/4 protein levels.	cinobufagin	13-24	SRY-box transcription factor 2	Homo sapiens	110-115
31824138-14	2019	In addition, cinobufagin ameliorated the proportion of CD133-positive cells, the size of spheroids and Nanog, Sox-2 and Oct3/4 protein levels.	cinobufagin	13-24	POU class 5 homeobox 1	Homo sapiens	120-126
31824138-16	2019	From a mechanistic point of view, cinobufagin was shown to inhibit IL-6-OPN-STAT3 signaling pathway.	cinobufagin	34-45	interleukin 6	Homo sapiens	67-71
31824138-16	2019	From a mechanistic point of view, cinobufagin was shown to inhibit IL-6-OPN-STAT3 signaling pathway.	cinobufagin	34-45	secreted phosphoprotein 1	Homo sapiens	72-75
31824138-16	2019	From a mechanistic point of view, cinobufagin was shown to inhibit IL-6-OPN-STAT3 signaling pathway.	cinobufagin	34-45	signal transducer and activator of transcription 3	Homo sapiens	76-81
31824138-18	2019	Conclusion: Collectively, our data demonstrated that cinobufagin inhibited the viability and tumorigenesis capability of osteosarcoma cells by blocking IL-6- OPN-STAT3 signaling pathway.	cinobufagin	53-64	interleukin 6	Homo sapiens	152-156
31824138-18	2019	Conclusion: Collectively, our data demonstrated that cinobufagin inhibited the viability and tumorigenesis capability of osteosarcoma cells by blocking IL-6- OPN-STAT3 signaling pathway.	cinobufagin	53-64	secreted phosphoprotein 1	Homo sapiens	158-161
31824138-18	2019	Conclusion: Collectively, our data demonstrated that cinobufagin inhibited the viability and tumorigenesis capability of osteosarcoma cells by blocking IL-6- OPN-STAT3 signaling pathway.	cinobufagin	53-64	signal transducer and activator of transcription 3	Homo sapiens	162-167
31572194-8	2019	The in vitro experiments showed that cinobufagin suppresses TGF-beta1/Smad3 signaling in a dose-dependent manner, attenuates the activation and differentiation of lung fibroblasts and inhibits EMT induced by TGF-beta1 in alveolar epithelial cells.	cinobufagin	37-48	transforming growth factor, beta 1	Mus musculus	60-69
31572194-8	2019	The in vitro experiments showed that cinobufagin suppresses TGF-beta1/Smad3 signaling in a dose-dependent manner, attenuates the activation and differentiation of lung fibroblasts and inhibits EMT induced by TGF-beta1 in alveolar epithelial cells.	cinobufagin	37-48	SMAD family member 3	Mus musculus	70-75
31572194-8	2019	The in vitro experiments showed that cinobufagin suppresses TGF-beta1/Smad3 signaling in a dose-dependent manner, attenuates the activation and differentiation of lung fibroblasts and inhibits EMT induced by TGF-beta1 in alveolar epithelial cells.	cinobufagin	37-48	transforming growth factor, beta 1	Mus musculus	208-217
30247877-0	2019	Alpha-7 Nicotinic Receptor-Targeted Cinobufagin Induces Antinociception and Inhibits NF-kappaB Signaling Pathway in DRG Neurons.	cinobufagin	36-47	cholinergic receptor, nicotinic, alpha polypeptide 7	Mus musculus	0-26
31552178-5	2019	Moreover, cinobufagin clearly inhibited the levels of phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), AKT, p-AKT, and B-cell lymphoma 2 (Bcl-2).	cinobufagin	10-21	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta	Homo sapiens	54-79
31552178-5	2019	Moreover, cinobufagin clearly inhibited the levels of phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), AKT, p-AKT, and B-cell lymphoma 2 (Bcl-2).	cinobufagin	10-21	AKT serine/threonine kinase 1	Homo sapiens	118-121
31552178-5	2019	Moreover, cinobufagin clearly inhibited the levels of phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), AKT, p-AKT, and B-cell lymphoma 2 (Bcl-2).	cinobufagin	10-21	AKT serine/threonine kinase 1	Homo sapiens	125-128
31552178-5	2019	Moreover, cinobufagin clearly inhibited the levels of phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), AKT, p-AKT, and B-cell lymphoma 2 (Bcl-2).	cinobufagin	10-21	BCL2 apoptosis regulator	Homo sapiens	134-151
31552178-5	2019	Moreover, cinobufagin clearly inhibited the levels of phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), AKT, p-AKT, and B-cell lymphoma 2 (Bcl-2).	cinobufagin	10-21	BCL2 apoptosis regulator	Homo sapiens	153-158
31091577-1	2019	Objective: To evaluate the analgesic effects of cinobufagin (CBG) on cancer-induced bone pain in rat and study the role of the muscarinic receptor M4 subtype (M4 mAChR) in its involvement.	cinobufagin	48-59	serpin family A member 6	Rattus norvegicus	61-64
31091577-20	2019	Conclusions: These results demonstrated that M4mAChR participated in mediating the alleviation of hyperalgesia by cinobufagin in rats with bone cancer pain, and its mechanism may be related to pCaMKIIa/CaMKIIa signaling pathway.	cinobufagin	114-125	calcium/calmodulin-dependent protein kinase II alpha	Rattus norvegicus	194-201
30839155-0	2019	Cinobufagin suppresses colorectal cancer angiogenesis by disrupting the endothelial mammalian target of rapamycin/hypoxia-inducible factor 1alpha axis.	cinobufagin	0-11	mechanistic target of rapamycin kinase	Homo sapiens	84-113
30839155-0	2019	Cinobufagin suppresses colorectal cancer angiogenesis by disrupting the endothelial mammalian target of rapamycin/hypoxia-inducible factor 1alpha axis.	cinobufagin	0-11	hypoxia inducible factor 1 subunit alpha	Homo sapiens	114-145
30839155-8	2019	Endothelial apoptosis is triggered by cinobufagin by stimulation of Bax and cascade activation of caspase 9 and caspase 3.	cinobufagin	38-49	BCL2 associated X, apoptosis regulator	Homo sapiens	68-71
30839155-8	2019	Endothelial apoptosis is triggered by cinobufagin by stimulation of Bax and cascade activation of caspase 9 and caspase 3.	cinobufagin	38-49	caspase 9	Homo sapiens	98-107
30839155-8	2019	Endothelial apoptosis is triggered by cinobufagin by stimulation of Bax and cascade activation of caspase 9 and caspase 3.	cinobufagin	38-49	caspase 3	Homo sapiens	112-121
30839155-11	2019	In conclusion, cinobufagin suppresses tumor neovascularization by disrupting the endothelial mTOR/HIF-1alpha pathway to trigger ROS-mediated vascular endothelial cell apoptosis.	cinobufagin	15-26	mechanistic target of rapamycin kinase	Homo sapiens	93-97
30839155-11	2019	In conclusion, cinobufagin suppresses tumor neovascularization by disrupting the endothelial mTOR/HIF-1alpha pathway to trigger ROS-mediated vascular endothelial cell apoptosis.	cinobufagin	15-26	hypoxia inducible factor 1 subunit alpha	Homo sapiens	98-108
30942456-0	2019	The anticancer effects of cinobufagin on hepatocellular carcinoma Huh-7 cells are associated with activation of the p73 signaling pathway.	cinobufagin	26-37	tumor protein p73	Homo sapiens	116-119
30942456-1	2019	The Na+/K+-ATPase inhibitor cinobufagin exhibits numerous anticancer effects on hepatocellular carcinoma (HCC) cells expressing wild-type p53 via inhibition of aurora kinase A (AURKA) and activation of p53 signaling.	cinobufagin	28-39	tumor protein p53	Homo sapiens	138-141
30942456-1	2019	The Na+/K+-ATPase inhibitor cinobufagin exhibits numerous anticancer effects on hepatocellular carcinoma (HCC) cells expressing wild-type p53 via inhibition of aurora kinase A (AURKA) and activation of p53 signaling.	cinobufagin	28-39	aurora kinase A	Homo sapiens	160-175
30942456-1	2019	The Na+/K+-ATPase inhibitor cinobufagin exhibits numerous anticancer effects on hepatocellular carcinoma (HCC) cells expressing wild-type p53 via inhibition of aurora kinase A (AURKA) and activation of p53 signaling.	cinobufagin	28-39	aurora kinase A	Homo sapiens	177-182
30942456-1	2019	The Na+/K+-ATPase inhibitor cinobufagin exhibits numerous anticancer effects on hepatocellular carcinoma (HCC) cells expressing wild-type p53 via inhibition of aurora kinase A (AURKA) and activation of p53 signaling.	cinobufagin	28-39	tumor protein p53	Homo sapiens	202-205
30942456-7	2019	Overexpression or inhibition of AURKA suppressed or promoted the anticancer effects of cinobufagin on Huh-7 cells, respectively.	cinobufagin	87-98	aurora kinase A	Homo sapiens	32-37
30942456-8	2019	These results indicated that cinobufagin may induce anticancer effects on Huh-7 cells via the inhibition of AURKA and p53 signaling, and via the activation of p73 signaling, in an AURKA-dependent manner.	cinobufagin	29-40	aurora kinase A	Homo sapiens	108-113
30942456-8	2019	These results indicated that cinobufagin may induce anticancer effects on Huh-7 cells via the inhibition of AURKA and p53 signaling, and via the activation of p73 signaling, in an AURKA-dependent manner.	cinobufagin	29-40	tumor protein p53	Homo sapiens	118-121
30942456-8	2019	These results indicated that cinobufagin may induce anticancer effects on Huh-7 cells via the inhibition of AURKA and p53 signaling, and via the activation of p73 signaling, in an AURKA-dependent manner.	cinobufagin	29-40	tumor protein p73	Homo sapiens	159-162
30942456-8	2019	These results indicated that cinobufagin may induce anticancer effects on Huh-7 cells via the inhibition of AURKA and p53 signaling, and via the activation of p73 signaling, in an AURKA-dependent manner.	cinobufagin	29-40	aurora kinase A	Homo sapiens	180-185
31301417-0	2019	Cinobufagin induced cell apoptosis and protective autophagy through the ROS/MAPK signaling pathway.	cinobufagin	0-11	mitogen-activated protein kinase 3	Homo sapiens	76-80
31301417-12	2019	In addition, treatment with cinobufagin could dramatically increase the expression of ROS and then activate the phosphorylation of MAPK family proteins, including ERK 1/2, JNK and p38.	cinobufagin	28-39	mitogen-activated protein kinase 3	Homo sapiens	131-135
31301417-12	2019	In addition, treatment with cinobufagin could dramatically increase the expression of ROS and then activate the phosphorylation of MAPK family proteins, including ERK 1/2, JNK and p38.	cinobufagin	28-39	mitogen-activated protein kinase 3	Homo sapiens	163-170
31301417-12	2019	In addition, treatment with cinobufagin could dramatically increase the expression of ROS and then activate the phosphorylation of MAPK family proteins, including ERK 1/2, JNK and p38.	cinobufagin	28-39	mitogen-activated protein kinase 8	Homo sapiens	172-175
31301417-12	2019	In addition, treatment with cinobufagin could dramatically increase the expression of ROS and then activate the phosphorylation of MAPK family proteins, including ERK 1/2, JNK and p38.	cinobufagin	28-39	mitogen-activated protein kinase 1	Homo sapiens	180-183
31301417-13	2019	What"s more, the reaction of apoptosis and autophagy induced by cinobufagin treatment could be reversed by p38 inhibitor SB203580 and JNK inhibitor SP600125 as well as ROS exclusive inhibitor antioxidant N-acetyl cysteine (NAC).	cinobufagin	64-75	mitogen-activated protein kinase 1	Homo sapiens	107-110
31301417-13	2019	What"s more, the reaction of apoptosis and autophagy induced by cinobufagin treatment could be reversed by p38 inhibitor SB203580 and JNK inhibitor SP600125 as well as ROS exclusive inhibitor antioxidant N-acetyl cysteine (NAC).	cinobufagin	64-75	mitogen-activated protein kinase 8	Homo sapiens	134-137
31301417-14	2019	CONCLUSIONS: Our findings provide clues concluding that cinobufagin could induce cell apoptosis and protective autophagy through the ROS/MAPK signaling pathway in human ovarian cancer cells.	cinobufagin	56-67	mitogen-activated protein kinase 3	Homo sapiens	137-141
30247877-0	2019	Alpha-7 Nicotinic Receptor-Targeted Cinobufagin Induces Antinociception and Inhibits NF-kappaB Signaling Pathway in DRG Neurons.	cinobufagin	36-47	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	85-94
30247877-4	2019	As shown in the hot-plate test, formalin test, and acetic acid writhing test in mice, administration of CBG produced significant antinociceptive activity in a dose-dependent manner, and the antinociceptive effect was blocked by intraperitoneal pretreatment of methyllycaconitine citrate (an alpha7 nicotinic receptor antagonist) and intrathecal delivery of an alpha7 nicotinic receptor antagonist siRNA (alpha7-siRNA).	cinobufagin	104-107	cholinergic receptor, nicotinic, alpha polypeptide 7	Mus musculus	291-316
30247877-4	2019	As shown in the hot-plate test, formalin test, and acetic acid writhing test in mice, administration of CBG produced significant antinociceptive activity in a dose-dependent manner, and the antinociceptive effect was blocked by intraperitoneal pretreatment of methyllycaconitine citrate (an alpha7 nicotinic receptor antagonist) and intrathecal delivery of an alpha7 nicotinic receptor antagonist siRNA (alpha7-siRNA).	cinobufagin	104-107	cholinergic receptor, nicotinic, alpha polypeptide 7	Mus musculus	360-385
30247877-6	2019	In the chemical pain models and primary cultured DRG neurons, Western blot analysis showed that the formation of p-IkappaB and p-NF-kappaB was regulated by CBG, and the effect of CBG was inhibited by alpha7-siRNA, and ELISA analysis indicated that CBG also regulated the expression of inflammatory cytokines through the alpha7 nicotinic receptor in DRG.	cinobufagin	156-159	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	129-138
30247877-6	2019	In the chemical pain models and primary cultured DRG neurons, Western blot analysis showed that the formation of p-IkappaB and p-NF-kappaB was regulated by CBG, and the effect of CBG was inhibited by alpha7-siRNA, and ELISA analysis indicated that CBG also regulated the expression of inflammatory cytokines through the alpha7 nicotinic receptor in DRG.	cinobufagin	179-182	cholinergic receptor, nicotinic, alpha polypeptide 7	Mus musculus	320-345
30247877-6	2019	In the chemical pain models and primary cultured DRG neurons, Western blot analysis showed that the formation of p-IkappaB and p-NF-kappaB was regulated by CBG, and the effect of CBG was inhibited by alpha7-siRNA, and ELISA analysis indicated that CBG also regulated the expression of inflammatory cytokines through the alpha7 nicotinic receptor in DRG.	cinobufagin	179-182	cholinergic receptor, nicotinic, alpha polypeptide 7	Mus musculus	320-345
30247877-7	2019	These results suggest that CBG may activate an alpha7 nicotinic receptor, thereby triggering the inhibition of the DRG NF-kappaB signaling pathway, resulting in an antinociceptive effect in mice.	cinobufagin	27-30	cholinergic receptor, nicotinic, alpha polypeptide 7	Mus musculus	47-72
30247877-7	2019	These results suggest that CBG may activate an alpha7 nicotinic receptor, thereby triggering the inhibition of the DRG NF-kappaB signaling pathway, resulting in an antinociceptive effect in mice.	cinobufagin	27-30	nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105	Mus musculus	119-128
31474710-0	2019	Cinobufagin Promotes Cell Cycle Arrest and Apoptosis to Block Human Esophageal Squamous Cell Carcinoma Cells Growth via the p73 Signalling Pathway.	cinobufagin	0-11	tumor protein p73	Homo sapiens	124-127
31474710-10	2019	Other data further showed that cinobufagin increased p73 expression and decreased Mdm2 expression, whereas p53 expression was not significantly changed.	cinobufagin	31-42	tumor protein p73	Homo sapiens	53-56
31474710-10	2019	Other data further showed that cinobufagin increased p73 expression and decreased Mdm2 expression, whereas p53 expression was not significantly changed.	cinobufagin	31-42	MDM2 proto-oncogene	Homo sapiens	82-86
31474710-11	2019	Taken together, these results suggest that growth inhibition of cinobufagin in esophageal cancer cells might act through the p73 pathway and its downstream molecules.	cinobufagin	64-75	tumor protein p73	Homo sapiens	125-128
28412840-5	2018	In addition, further molecular mechanistic investigation demonstrated that cinobufagin significantly increased Bax expression, decreased Bcl-2 expression level and up-regulated the ratio of the pro-apoptosis/anti-apoptosis protein Bax/Bcl-2, which were demonstrated by RT-qPCR and western blot assays.	cinobufagin	75-86	BCL2 associated X, apoptosis regulator	Homo sapiens	111-114
29359345-6	2018	The release of mediators of anaphylaxis results showed cinobufagin and osthole can cause anaphylactoid reactions by triggering the release of beta-hexosaminidase and histamine via IgE-R. Praeruptorin A and schizandrin A could promote the release of beta-hexosaminidase and histamine via MrgprX2 receptor.	cinobufagin	55-66	O-GlcNAcase	Rattus norvegicus	142-161
29359345-6	2018	The release of mediators of anaphylaxis results showed cinobufagin and osthole can cause anaphylactoid reactions by triggering the release of beta-hexosaminidase and histamine via IgE-R. Praeruptorin A and schizandrin A could promote the release of beta-hexosaminidase and histamine via MrgprX2 receptor.	cinobufagin	55-66	O-GlcNAcase	Rattus norvegicus	249-268
29359345-6	2018	The release of mediators of anaphylaxis results showed cinobufagin and osthole can cause anaphylactoid reactions by triggering the release of beta-hexosaminidase and histamine via IgE-R. Praeruptorin A and schizandrin A could promote the release of beta-hexosaminidase and histamine via MrgprX2 receptor.	cinobufagin	55-66	MAS related GPR family member X2	Rattus norvegicus	287-294
28412840-5	2018	In addition, further molecular mechanistic investigation demonstrated that cinobufagin significantly increased Bax expression, decreased Bcl-2 expression level and up-regulated the ratio of the pro-apoptosis/anti-apoptosis protein Bax/Bcl-2, which were demonstrated by RT-qPCR and western blot assays.	cinobufagin	75-86	BCL2 apoptosis regulator	Homo sapiens	137-142
28412840-5	2018	In addition, further molecular mechanistic investigation demonstrated that cinobufagin significantly increased Bax expression, decreased Bcl-2 expression level and up-regulated the ratio of the pro-apoptosis/anti-apoptosis protein Bax/Bcl-2, which were demonstrated by RT-qPCR and western blot assays.	cinobufagin	75-86	BCL2 associated X, apoptosis regulator	Homo sapiens	231-234
28412840-5	2018	In addition, further molecular mechanistic investigation demonstrated that cinobufagin significantly increased Bax expression, decreased Bcl-2 expression level and up-regulated the ratio of the pro-apoptosis/anti-apoptosis protein Bax/Bcl-2, which were demonstrated by RT-qPCR and western blot assays.	cinobufagin	75-86	BCL2 apoptosis regulator	Homo sapiens	235-240
28184922-0	2017	Reversal of P-gp-mediated multidrug resistance in colon cancer by cinobufagin.	cinobufagin	66-77	ATP binding cassette subfamily B member 1	Homo sapiens	12-16
29669353-15	2018	The effects of cinobufagin on cell proliferation, apoptosis, ROS generation and DeltaPsim loss were dramatically reversed when the cells were pretreated with the thiol-antioxidants NAC or GSH.	cinobufagin	15-26	X-linked Kx blood group	Homo sapiens	181-184
29669353-16	2018	Moreover, cinobufagin treatment increased the expression of the pro-apoptotic protein Bax and decreased the expression of the anti-apoptitic protein Bcl-2, thus altering the ratio of Bax to Bcl-2.	cinobufagin	10-21	BCL2 associated X, apoptosis regulator	Homo sapiens	86-89
29669353-16	2018	Moreover, cinobufagin treatment increased the expression of the pro-apoptotic protein Bax and decreased the expression of the anti-apoptitic protein Bcl-2, thus altering the ratio of Bax to Bcl-2.	cinobufagin	10-21	BCL2 apoptosis regulator	Homo sapiens	149-154
29669353-16	2018	Moreover, cinobufagin treatment increased the expression of the pro-apoptotic protein Bax and decreased the expression of the anti-apoptitic protein Bcl-2, thus altering the ratio of Bax to Bcl-2.	cinobufagin	10-21	BCL2 associated X, apoptosis regulator	Homo sapiens	183-186
29669353-16	2018	Moreover, cinobufagin treatment increased the expression of the pro-apoptotic protein Bax and decreased the expression of the anti-apoptitic protein Bcl-2, thus altering the ratio of Bax to Bcl-2.	cinobufagin	10-21	BCL2 apoptosis regulator	Homo sapiens	190-195
29669353-17	2018	Furthermore, Cinobufagin treatment caused cytochrome c release from the mitochondria to cytoplasm, thus increasing the protein levels of cleaved-caspase family members to induce apoptosis.	cinobufagin	13-24	cytochrome c, somatic	Homo sapiens	42-54
28002791-21	2017	Gene expression of POMC and CTSL in cinobufagin group was significantly up-regulated comparing to the control group.	cinobufagin	36-47	pro-opiomelanocortin-alpha	Mus musculus	19-23
28002791-21	2017	Gene expression of POMC and CTSL in cinobufagin group was significantly up-regulated comparing to the control group.	cinobufagin	36-47	cathepsin L	Mus musculus	28-32
28002791-0	2017	Chinese herb cinobufagin-reduced cancer pain is associated with increased peripheral opioids by invaded CD3/4/8 lymphocytes.	cinobufagin	13-24	CD34 antigen	Mus musculus	104-111
28002791-23	2017	CONCLUSIONS: Cinobufagin-induced local analgesic effect might be associated with increased activity of POMC/beta-END/mu-OR pathway released from invaded CD3/4/8 lymphocytes in cancer tissues.	cinobufagin	13-24	pro-opiomelanocortin-alpha	Mus musculus	103-107
28002791-16	2017	The expression of beta-END and CRF in the plasma and tumor tissues of cinobufagin group were much higher than that of the model group mice, but the expression of IL-1beta in the plasma and tumor tissues was much lower than that in the model group mice.	cinobufagin	70-81	pro-opiomelanocortin-alpha	Mus musculus	18-26
28002791-23	2017	CONCLUSIONS: Cinobufagin-induced local analgesic effect might be associated with increased activity of POMC/beta-END/mu-OR pathway released from invaded CD3/4/8 lymphocytes in cancer tissues.	cinobufagin	13-24	pro-opiomelanocortin-alpha	Mus musculus	108-116
28002791-17	2017	Meanwhile, the expression of beta-END, POMC and mu-OR proteins was significantly increased in the xenograft tissues from cinobufagin group.	cinobufagin	121-132	pro-opiomelanocortin-alpha	Mus musculus	29-37
28002791-17	2017	Meanwhile, the expression of beta-END, POMC and mu-OR proteins was significantly increased in the xenograft tissues from cinobufagin group.	cinobufagin	121-132	pro-opiomelanocortin-alpha	Mus musculus	39-43
28002791-23	2017	CONCLUSIONS: Cinobufagin-induced local analgesic effect might be associated with increased activity of POMC/beta-END/mu-OR pathway released from invaded CD3/4/8 lymphocytes in cancer tissues.	cinobufagin	13-24	opioid receptor, mu 1	Mus musculus	117-122
28002791-17	2017	Meanwhile, the expression of beta-END, POMC and mu-OR proteins was significantly increased in the xenograft tissues from cinobufagin group.	cinobufagin	121-132	opioid receptor, mu 1	Mus musculus	48-53
28002791-23	2017	CONCLUSIONS: Cinobufagin-induced local analgesic effect might be associated with increased activity of POMC/beta-END/mu-OR pathway released from invaded CD3/4/8 lymphocytes in cancer tissues.	cinobufagin	13-24	CD34 antigen	Mus musculus	153-160
28002791-19	2017	In the cell co-culture assays, the content of beta-END in the supernatant was significantly increased by cinobufagin in a dose-dependent manner.	cinobufagin	105-116	pro-opiomelanocortin-alpha	Mus musculus	46-54
26959116-0	2016	Cinobufagin inhibits tumor growth by inducing intrinsic apoptosis through AKT signaling pathway in human nonsmall cell lung cancer cells.	cinobufagin	0-11	AKT serine/threonine kinase 1	Homo sapiens	74-77
27574776-5	2016	The results showed that CBG enhanced FIST-specific IgG and IgG2a, the levels of interferon-gamma (IFNgamma) and nitric oxide (NO), and the splenocyte proliferation response induced by concanavalin A, lipopolysaccharide, and FIST.	cinobufagin	24-27	immunoglobulin heavy variable V1-9	Mus musculus	59-64
27574776-5	2016	The results showed that CBG enhanced FIST-specific IgG and IgG2a, the levels of interferon-gamma (IFNgamma) and nitric oxide (NO), and the splenocyte proliferation response induced by concanavalin A, lipopolysaccharide, and FIST.	cinobufagin	24-27	interferon gamma	Mus musculus	80-96
27574776-5	2016	The results showed that CBG enhanced FIST-specific IgG and IgG2a, the levels of interferon-gamma (IFNgamma) and nitric oxide (NO), and the splenocyte proliferation response induced by concanavalin A, lipopolysaccharide, and FIST.	cinobufagin	24-27	interferon gamma	Mus musculus	98-106
27845066-0	2017	Cinobufagin induces apoptosis of osteosarcoma cells through inactivation of Notch signaling.	cinobufagin	0-11	notch 1	Mus musculus	76-81
27845066-6	2017	The involvement of Notch signaling in Cinobufagin-induced apoptosis was confirmed using gain and loss-of function assays.	cinobufagin	38-49	notch 1	Mus musculus	19-24
27845066-9	2017	Cinobufagin treatment decreased the expression of Notch-1, and Hes-1, Hes-5 and Hey-1 gene expression in OS cell lines.	cinobufagin	0-11	notch 1	Mus musculus	50-57
27845066-9	2017	Cinobufagin treatment decreased the expression of Notch-1, and Hes-1, Hes-5 and Hey-1 gene expression in OS cell lines.	cinobufagin	0-11	hes family bHLH transcription factor 1	Mus musculus	63-68
27845066-9	2017	Cinobufagin treatment decreased the expression of Notch-1, and Hes-1, Hes-5 and Hey-1 gene expression in OS cell lines.	cinobufagin	0-11	hes family bHLH transcription factor 5	Mus musculus	70-75
27845066-9	2017	Cinobufagin treatment decreased the expression of Notch-1, and Hes-1, Hes-5 and Hey-1 gene expression in OS cell lines.	cinobufagin	0-11	hairy/enhancer-of-split related with YRPW motif 1	Mus musculus	80-85
27845066-10	2017	Furthermore, Notch activation attenuated the Cinobufagin-induced apoptosis, while Notch inhibition enhanced this effect.	cinobufagin	45-56	notch 1	Mus musculus	13-18
27845066-13	2017	Taken together, our data suggested that Cinobufagin inhibited cell survival and induced apoptosis in OS cells both in vitro and in vivo, and these effects were partly mediated through the Notch pathway.	cinobufagin	40-51	notch 1	Mus musculus	188-193
27894091-4	2017	At the signaling level, CBG treatment in CRC cells provoked endoplasmic reticulum stress (ER stress), the latter was evidenced by caspase-12 activation, CHOP expression, as well as PERK and IRE1 phosphorylations.	cinobufagin	24-27	DNA damage inducible transcript 3	Homo sapiens	153-157
27894091-4	2017	At the signaling level, CBG treatment in CRC cells provoked endoplasmic reticulum stress (ER stress), the latter was evidenced by caspase-12 activation, CHOP expression, as well as PERK and IRE1 phosphorylations.	cinobufagin	24-27	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	181-185
27894091-4	2017	At the signaling level, CBG treatment in CRC cells provoked endoplasmic reticulum stress (ER stress), the latter was evidenced by caspase-12 activation, CHOP expression, as well as PERK and IRE1 phosphorylations.	cinobufagin	24-27	endoplasmic reticulum to nucleus signaling 1	Homo sapiens	190-194
27894091-5	2017	Contrarily, the ER stress inhibitor salubrinal, the caspase-12 inhibitor and CHOP shRNA remarkably attenuated CBG-induced CRC cell death and apoptosis.	cinobufagin	110-113	DNA damage inducible transcript 3	Homo sapiens	77-81
27894091-6	2017	Further, CBG in-activated mammalian target or rapamycin complex 1 (mTORC1), which appeared responsible for proliferation inhibition in CRC cells.	cinobufagin	9-12	CREB regulated transcription coactivator 1	Mus musculus	67-73
27894091-9	2017	CHOP upregulation and mTORC1 in-activation were also noticed in CBG-treated HCT-116 tumors.	cinobufagin	64-67	DNA damage inducible transcript 3	Homo sapiens	0-4
27894091-9	2017	CHOP upregulation and mTORC1 in-activation were also noticed in CBG-treated HCT-116 tumors.	cinobufagin	64-67	CREB regulated transcription coactivator 1	Mus musculus	22-28
27529866-5	2016	Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3.	cinobufagin	154-157	caspase 3	Homo sapiens	228-237
27176794-0	2016	Cinobufagin induces autophagy-mediated cell death in human osteosarcoma U2OS cells through the ROS/JNK/p38 signaling pathway.	cinobufagin	0-11	mitogen-activated protein kinase 8	Homo sapiens	99-102
27176794-0	2016	Cinobufagin induces autophagy-mediated cell death in human osteosarcoma U2OS cells through the ROS/JNK/p38 signaling pathway.	cinobufagin	0-11	mitogen-activated protein kinase 14	Homo sapiens	103-106
27176794-9	2016	Exposure to cinobufagin resulted in the activation of caspase-3, -8, -9, as well as cleaved PARP which indicated that cinobufagin induced caspase-dependent apoptosis.	cinobufagin	12-23	caspase 3	Homo sapiens	54-71
27176794-9	2016	Exposure to cinobufagin resulted in the activation of caspase-3, -8, -9, as well as cleaved PARP which indicated that cinobufagin induced caspase-dependent apoptosis.	cinobufagin	12-23	poly(ADP-ribose) polymerase 1	Homo sapiens	92-96
27176794-9	2016	Exposure to cinobufagin resulted in the activation of caspase-3, -8, -9, as well as cleaved PARP which indicated that cinobufagin induced caspase-dependent apoptosis.	cinobufagin	118-129	poly(ADP-ribose) polymerase 1	Homo sapiens	92-96
27176794-13	2016	Cinobufagin also induced phosphorylation of the JNK and p38 signaling pathway as well as ROS generation.	cinobufagin	0-11	mitogen-activated protein kinase 8	Homo sapiens	48-51
27176794-13	2016	Cinobufagin also induced phosphorylation of the JNK and p38 signaling pathway as well as ROS generation.	cinobufagin	0-11	mitogen-activated protein kinase 14	Homo sapiens	56-59
27176794-16	2016	Our research proved that cinobufagin triggered apoptosis and autophagic cell death via activation of the ROS/JNK/p-38 axis.	cinobufagin	25-36	mitogen-activated protein kinase 8	Homo sapiens	109-112
27176794-16	2016	Our research proved that cinobufagin triggered apoptosis and autophagic cell death via activation of the ROS/JNK/p-38 axis.	cinobufagin	25-36	mitogen-activated protein kinase 14	Homo sapiens	113-117