PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
20118535-0	2010	The resorcylic acid lactone hypothemycin selectively inhibits the mitogen-activated protein kinase kinase-extracellular signal-regulated kinase pathway in cells.	hypothemycin	28-40	Eph receptor B1	Rattus norvegicus	106-143
26371861-0	2015	Hypothemycin inhibits tumor necrosis factor-alpha production by tristetraprolin-dependent down-regulation of mRNA stability in lipopolysaccharide-stimulated macrophages.	hypothemycin	0-12	tumor necrosis factor	Homo sapiens	22-49
26371861-0	2015	Hypothemycin inhibits tumor necrosis factor-alpha production by tristetraprolin-dependent down-regulation of mRNA stability in lipopolysaccharide-stimulated macrophages.	hypothemycin	0-12	ZFP36 ring finger protein	Homo sapiens	64-79
26371861-2	2015	In the present study, we investigated the effect of hypothemycin on tumor necrosis factor-alpha (TNF-alpha) production in macrophages and the molecular mechanisms involved in this effect.	hypothemycin	52-64	tumor necrosis factor	Homo sapiens	68-95
26371861-2	2015	In the present study, we investigated the effect of hypothemycin on tumor necrosis factor-alpha (TNF-alpha) production in macrophages and the molecular mechanisms involved in this effect.	hypothemycin	52-64	tumor necrosis factor	Homo sapiens	97-106
26371861-3	2015	Hypothemycin potently suppressed the TNF-alpha production without affecting nitric oxide production in lipopolysaccharide (LPS)-stimulated macrophages.	hypothemycin	0-12	tumor necrosis factor	Homo sapiens	37-46
26371861-5	2015	Further study demonstrated that the stability of TNF-alpha mRNA was decreased by hypothemycin treatment.	hypothemycin	81-93	tumor necrosis factor	Homo sapiens	49-58
26371861-6	2015	In addition, hypothemycin suppressed LPS-induced phosphorylation of p38 MAPK and ERK.	hypothemycin	13-25	mitogen-activated protein kinase 14	Homo sapiens	68-71
26371861-6	2015	In addition, hypothemycin suppressed LPS-induced phosphorylation of p38 MAPK and ERK.	hypothemycin	13-25	mitogen-activated protein kinase 1	Homo sapiens	72-76
26371861-6	2015	In addition, hypothemycin suppressed LPS-induced phosphorylation of p38 MAPK and ERK.	hypothemycin	13-25	mitogen-activated protein kinase 1	Homo sapiens	81-84
26371861-7	2015	Moreover, knockdown of tristetraprolin (TTP), which is an important trans-acting regulator of TNF-alpha mRNA stability and downstream target of p38 MAPK and ERK, reversed hypothemycin-mediated inhibition of TNF-alpha mRNA expression.	hypothemycin	171-183	ZFP36 ring finger protein	Homo sapiens	23-38
26371861-7	2015	Moreover, knockdown of tristetraprolin (TTP), which is an important trans-acting regulator of TNF-alpha mRNA stability and downstream target of p38 MAPK and ERK, reversed hypothemycin-mediated inhibition of TNF-alpha mRNA expression.	hypothemycin	171-183	ZFP36 ring finger protein	Homo sapiens	40-43
26371861-7	2015	Moreover, knockdown of tristetraprolin (TTP), which is an important trans-acting regulator of TNF-alpha mRNA stability and downstream target of p38 MAPK and ERK, reversed hypothemycin-mediated inhibition of TNF-alpha mRNA expression.	hypothemycin	171-183	tumor necrosis factor	Homo sapiens	94-103
26371861-7	2015	Moreover, knockdown of tristetraprolin (TTP), which is an important trans-acting regulator of TNF-alpha mRNA stability and downstream target of p38 MAPK and ERK, reversed hypothemycin-mediated inhibition of TNF-alpha mRNA expression.	hypothemycin	171-183	mitogen-activated protein kinase 14	Homo sapiens	144-147
26371861-7	2015	Moreover, knockdown of tristetraprolin (TTP), which is an important trans-acting regulator of TNF-alpha mRNA stability and downstream target of p38 MAPK and ERK, reversed hypothemycin-mediated inhibition of TNF-alpha mRNA expression.	hypothemycin	171-183	mitogen-activated protein kinase 1	Homo sapiens	148-152
26371861-7	2015	Moreover, knockdown of tristetraprolin (TTP), which is an important trans-acting regulator of TNF-alpha mRNA stability and downstream target of p38 MAPK and ERK, reversed hypothemycin-mediated inhibition of TNF-alpha mRNA expression.	hypothemycin	171-183	mitogen-activated protein kinase 1	Homo sapiens	157-160
26371861-7	2015	Moreover, knockdown of tristetraprolin (TTP), which is an important trans-acting regulator of TNF-alpha mRNA stability and downstream target of p38 MAPK and ERK, reversed hypothemycin-mediated inhibition of TNF-alpha mRNA expression.	hypothemycin	171-183	tumor necrosis factor	Homo sapiens	207-216
26371861-8	2015	Collectively, our results suggest that hypothemycin suppresses TNF-alpha production by TTP-dependent destabilization of TNF-alpha mRNA and this is mediated, at least in part, by blocking the activation of p38 MAPK and ERK.	hypothemycin	39-51	tumor necrosis factor	Homo sapiens	63-72
26371861-8	2015	Collectively, our results suggest that hypothemycin suppresses TNF-alpha production by TTP-dependent destabilization of TNF-alpha mRNA and this is mediated, at least in part, by blocking the activation of p38 MAPK and ERK.	hypothemycin	39-51	ZFP36 ring finger protein	Homo sapiens	87-90
26371861-8	2015	Collectively, our results suggest that hypothemycin suppresses TNF-alpha production by TTP-dependent destabilization of TNF-alpha mRNA and this is mediated, at least in part, by blocking the activation of p38 MAPK and ERK.	hypothemycin	39-51	tumor necrosis factor	Homo sapiens	120-129
26371861-8	2015	Collectively, our results suggest that hypothemycin suppresses TNF-alpha production by TTP-dependent destabilization of TNF-alpha mRNA and this is mediated, at least in part, by blocking the activation of p38 MAPK and ERK.	hypothemycin	39-51	mitogen-activated protein kinase 14	Homo sapiens	205-208
26371861-8	2015	Collectively, our results suggest that hypothemycin suppresses TNF-alpha production by TTP-dependent destabilization of TNF-alpha mRNA and this is mediated, at least in part, by blocking the activation of p38 MAPK and ERK.	hypothemycin	39-51	mitogen-activated protein kinase 1	Homo sapiens	209-213
26371861-8	2015	Collectively, our results suggest that hypothemycin suppresses TNF-alpha production by TTP-dependent destabilization of TNF-alpha mRNA and this is mediated, at least in part, by blocking the activation of p38 MAPK and ERK.	hypothemycin	39-51	mitogen-activated protein kinase 1	Homo sapiens	218-221
26107610-6	2015	Examination of these stabilizing compounds showed that three of these were analogs of hypothemycin, a known covalent allosteric MEK1 inhibitor, while the remaining compounds covered one structural class.	hypothemycin	86-98	mitogen-activated protein kinase kinase 1	Homo sapiens	128-132
20118535-1	2010	The resorcylic acid lactone hypothemycin has been shown to inactivate protein kinases by binding to a cysteine conserved in 46 protein kinases, including mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase (ERK) and platelet-derived growth factor receptor (PDGFR).	hypothemycin	28-40	Eph receptor B1	Rattus norvegicus	201-238
20118535-1	2010	The resorcylic acid lactone hypothemycin has been shown to inactivate protein kinases by binding to a cysteine conserved in 46 protein kinases, including mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase (ERK) and platelet-derived growth factor receptor (PDGFR).	hypothemycin	28-40	Eph receptor B1	Rattus norvegicus	240-243
20118535-3	2010	Hypothemycin normalized the morphology and inhibited anchorage-independent growth of Ki-ras transformed normal rat kidney (NRK) cells with selectivity and potency comparable to or greater than that of the MEK inhibitor U0126.	hypothemycin	0-12	KRAS proto-oncogene, GTPase	Rattus norvegicus	85-91
20118535-4	2010	In Ki-ras-transformed and phorbol 12-myristate 13-acetate (PMA)-treated NRK cells, hypothemycin blocked ERK activation but showed a minimal effect on autophosphorylation of protein kinase D1 (PKD1), another kinase containing the conserved cysteine.	hypothemycin	83-95	KRAS proto-oncogene, GTPase	Rattus norvegicus	3-9
20118535-4	2010	In Ki-ras-transformed and phorbol 12-myristate 13-acetate (PMA)-treated NRK cells, hypothemycin blocked ERK activation but showed a minimal effect on autophosphorylation of protein kinase D1 (PKD1), another kinase containing the conserved cysteine.	hypothemycin	83-95	Eph receptor B1	Rattus norvegicus	104-107
20118535-4	2010	In Ki-ras-transformed and phorbol 12-myristate 13-acetate (PMA)-treated NRK cells, hypothemycin blocked ERK activation but showed a minimal effect on autophosphorylation of protein kinase D1 (PKD1), another kinase containing the conserved cysteine.	hypothemycin	83-95	protein kinase D1	Rattus norvegicus	173-190
20118535-4	2010	In Ki-ras-transformed and phorbol 12-myristate 13-acetate (PMA)-treated NRK cells, hypothemycin blocked ERK activation but showed a minimal effect on autophosphorylation of protein kinase D1 (PKD1), another kinase containing the conserved cysteine.	hypothemycin	83-95	protein kinase D1	Rattus norvegicus	192-196
20118535-5	2010	Hypothemycin potently inhibited PDGFR autophosphorylation and activation of the MEK-ERK pathway in platelet-derived growth factor (PDGF)-treated NRK cells.	hypothemycin	0-12	Eph receptor B1	Rattus norvegicus	84-87
20118535-7	2010	Hypothemycin also inhibited growth factor- and anchorage-independent growth of human cancer cell lines with a constitutively active MEK-ERK pathway.	hypothemycin	0-12	Eph receptor B1	Rattus norvegicus	136-139
20118535-8	2010	Although hypothemycin has the potential to inactivate various protein kinases, the results indicate that in intracellular environments, hypothemycin can inhibit the MEK-ERK axis with sufficient selectivity to normalize transformed phenotypes of cells dependent on this pathway.	hypothemycin	136-148	Eph receptor B1	Rattus norvegicus	169-172
17925481-5	2008	In contrast to imatinib, however, hypothemycin also effectively inhibited FcepsilonRI-mediated degranulation and cytokine production in addition to the potentiation of these responses via Kit.	hypothemycin	34-46	Fc receptor, IgE, high affinity I, alpha polypeptide	Mus musculus	74-85
18571434-0	2008	Molecular modeling and crystal structure of ERK2-hypothemycin complexes.	hypothemycin	49-61	mitogen-activated protein kinase 1	Homo sapiens	44-48
18571434-3	2008	As a paradigm for the structures of the cis-enone resorcylic acid lactone complexes with this subset of kinases, we have modeled the structure of ERK2-hypothemycin reversible and covalent complexes using docking and extended molecular dynamics simulations.	hypothemycin	151-163	mitogen-activated protein kinase 1	Homo sapiens	146-150
10598882-4	1999	Hypothemycin potently suppressed the production of IL-2 (IC50: 9 nM) but affected IL-2-induced proliferation to a lesser extent (IC50: 194 nM).	hypothemycin	0-12	interleukin 2	Homo sapiens	51-55
16537514-5	2006	Kinetic analyses showed time-dependent inhibition, a hallmark of covalent inactivation, and biochemical studies of the interaction of extracellular signal-regulated kinase (ERK)2 with hypothemycin confirmed covalent adduct formation.	hypothemycin	184-196	mitogen-activated protein kinase 1	Homo sapiens	134-178
16537514-7	2006	Cell lines dependent on the activation of Tyr kinase mitogen receptor targets of the resorcylic acid lactones were unusually sensitive toward hypothemycin and showed the expected inhibition of kinase phosphorylation due to inhibition of the mitogen receptors and/or MEK1/2 and ERK1/2.	hypothemycin	142-154	mitogen-activated protein kinase 3	Homo sapiens	277-283
16537514-8	2006	Among cells without mitogen receptor targets, those harboring an ERK pathway-activating B-RAF V600E mutation were selectively and potently inhibited by hypothemycin.	hypothemycin	152-164	mitogen-activated protein kinase 1	Homo sapiens	65-68
16537514-9	2006	Hypothemycin also prevented stimulated activation of the p38 cascade through inhibition of the Cys-containing targets MEK3/6 and TGF-beta-activated kinase 1 and of the JNK/SAPK (c-Jun N-terminal kinase/stress-activated protein kinase) cascade through inhibition of MEK4/7.	hypothemycin	0-12	mitogen-activated protein kinase 1	Homo sapiens	57-60
16537514-9	2006	Hypothemycin also prevented stimulated activation of the p38 cascade through inhibition of the Cys-containing targets MEK3/6 and TGF-beta-activated kinase 1 and of the JNK/SAPK (c-Jun N-terminal kinase/stress-activated protein kinase) cascade through inhibition of MEK4/7.	hypothemycin	0-12	mitogen-activated protein kinase kinase 3	Homo sapiens	118-124
16537514-9	2006	Hypothemycin also prevented stimulated activation of the p38 cascade through inhibition of the Cys-containing targets MEK3/6 and TGF-beta-activated kinase 1 and of the JNK/SAPK (c-Jun N-terminal kinase/stress-activated protein kinase) cascade through inhibition of MEK4/7.	hypothemycin	0-12	mitogen-activated protein kinase kinase kinase 7	Homo sapiens	129-156
16537514-9	2006	Hypothemycin also prevented stimulated activation of the p38 cascade through inhibition of the Cys-containing targets MEK3/6 and TGF-beta-activated kinase 1 and of the JNK/SAPK (c-Jun N-terminal kinase/stress-activated protein kinase) cascade through inhibition of MEK4/7.	hypothemycin	0-12	mitogen-activated protein kinase 8	Homo sapiens	168-176
16537514-9	2006	Hypothemycin also prevented stimulated activation of the p38 cascade through inhibition of the Cys-containing targets MEK3/6 and TGF-beta-activated kinase 1 and of the JNK/SAPK (c-Jun N-terminal kinase/stress-activated protein kinase) cascade through inhibition of MEK4/7.	hypothemycin	0-12	mitogen-activated protein kinase kinase 4	Homo sapiens	265-269
10598882-4	1999	Hypothemycin potently suppressed the production of IL-2 (IC50: 9 nM) but affected IL-2-induced proliferation to a lesser extent (IC50: 194 nM).	hypothemycin	0-12	interleukin 2	Homo sapiens	82-86
10598882-5	1999	Hypothemycin also inhibited IL-6, IL-10, IFN-gamma and TNF-alpha production.	hypothemycin	0-12	interleukin 6	Homo sapiens	28-32
10598882-5	1999	Hypothemycin also inhibited IL-6, IL-10, IFN-gamma and TNF-alpha production.	hypothemycin	0-12	interleukin 10	Homo sapiens	34-39
10598882-5	1999	Hypothemycin also inhibited IL-6, IL-10, IFN-gamma and TNF-alpha production.	hypothemycin	0-12	interferon gamma	Homo sapiens	41-50
10598882-5	1999	Hypothemycin also inhibited IL-6, IL-10, IFN-gamma and TNF-alpha production.	hypothemycin	0-12	tumor necrosis factor	Homo sapiens	55-64
10598882-8	1999	Analysis of the effect of hypothemycin on CD69 induction suggested that it disrupts calcineurin-independent rather than calcineurin-dependent signaling.	hypothemycin	26-38	CD69 molecule	Homo sapiens	42-46
10598882-9	1999	Furthermore, hypothemycin was able to inhibit the phosphorylation of ERK1/2 induced by PMA treatment of T cells.	hypothemycin	13-25	mitogen-activated protein kinase 3	Homo sapiens	69-75
10595743-3	1999	Treatment of tumor cells with hypothemycin resulted in reduced expression of Ras-inducible genes, including MMP (matrix metalloproteinase)-1, MMP-9, transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF), but not that of the constitutively expressed gene, MMP-2.	hypothemycin	30-42	matrix metallopeptidase 9	Mus musculus	142-147
10595743-3	1999	Treatment of tumor cells with hypothemycin resulted in reduced expression of Ras-inducible genes, including MMP (matrix metalloproteinase)-1, MMP-9, transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF), but not that of the constitutively expressed gene, MMP-2.	hypothemycin	30-42	vascular endothelial growth factor A	Mus musculus	197-231
10595743-3	1999	Treatment of tumor cells with hypothemycin resulted in reduced expression of Ras-inducible genes, including MMP (matrix metalloproteinase)-1, MMP-9, transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF), but not that of the constitutively expressed gene, MMP-2.	hypothemycin	30-42	vascular endothelial growth factor A	Mus musculus	233-237
10595743-3	1999	Treatment of tumor cells with hypothemycin resulted in reduced expression of Ras-inducible genes, including MMP (matrix metalloproteinase)-1, MMP-9, transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF), but not that of the constitutively expressed gene, MMP-2.	hypothemycin	30-42	matrix metallopeptidase 2	Mus musculus	291-296
10595743-4	1999	The results of zymography demonstrated that hypothemycin reduced the production of MMP-9 and MMP-3, another Ras-inducible MMP, in the culture medium.	hypothemycin	44-56	matrix metallopeptidase 9	Mus musculus	83-88
10595743-4	1999	The results of zymography demonstrated that hypothemycin reduced the production of MMP-9 and MMP-3, another Ras-inducible MMP, in the culture medium.	hypothemycin	44-56	matrix metallopeptidase 3	Mus musculus	93-98
10595743-8	1999	Since MMP-1, MMP-3 and MMP-9 play important roles in tumor invasion and TGF-beta and VEGF are involved in tumor angiogenesis, hypothemycin is considered to be an example of a new class of antitumor drugs, whose antitumor efficacy can be at least partly attributed to inhibition of Ras-inducible genes.	hypothemycin	126-138	matrix metallopeptidase 13	Mus musculus	6-11
10595743-8	1999	Since MMP-1, MMP-3 and MMP-9 play important roles in tumor invasion and TGF-beta and VEGF are involved in tumor angiogenesis, hypothemycin is considered to be an example of a new class of antitumor drugs, whose antitumor efficacy can be at least partly attributed to inhibition of Ras-inducible genes.	hypothemycin	126-138	matrix metallopeptidase 3	Mus musculus	13-18
10595743-8	1999	Since MMP-1, MMP-3 and MMP-9 play important roles in tumor invasion and TGF-beta and VEGF are involved in tumor angiogenesis, hypothemycin is considered to be an example of a new class of antitumor drugs, whose antitumor efficacy can be at least partly attributed to inhibition of Ras-inducible genes.	hypothemycin	126-138	matrix metallopeptidase 9	Mus musculus	23-28
10595743-8	1999	Since MMP-1, MMP-3 and MMP-9 play important roles in tumor invasion and TGF-beta and VEGF are involved in tumor angiogenesis, hypothemycin is considered to be an example of a new class of antitumor drugs, whose antitumor efficacy can be at least partly attributed to inhibition of Ras-inducible genes.	hypothemycin	126-138	vascular endothelial growth factor A	Mus musculus	85-89
10421424-0	1999	Suppression of oncogenic transformation by hypothemycin associated with accelerated cyclin D1 degradation through ubiquitin-proteasome pathway.	hypothemycin	43-55	cyclin D1	Mus musculus	84-93
10421424-2	1999	Here we report that treatment on v-K-ras-transformed NIH3T3 cells (DT cells) with hypothemycin caused drastic decrease in amount of cyclin D1 protein with concomitant prolongation of G1 phase in their cell cycle.	hypothemycin	82-94	cyclin D1	Mus musculus	132-141
10421424-3	1999	Analysis using hypothemycin-resistant mutant of Schizosaccharomyces pombe (S. pombe) was carried out to show that S. pombe rhp6+ (homologue of Saccharomyces cerevisiae RAD6) and mammalian ubiquitin-conjugating enzyme 2 (ubc2) are the targets of hypothemycin or its downstream molecules in ubiquitin-conjugation process.	hypothemycin	15-27	E2 ubiquitin-conjugating protein RAD6	Saccharomyces cerevisiae S288C	168-172
10421424-3	1999	Analysis using hypothemycin-resistant mutant of Schizosaccharomyces pombe (S. pombe) was carried out to show that S. pombe rhp6+ (homologue of Saccharomyces cerevisiae RAD6) and mammalian ubiquitin-conjugating enzyme 2 (ubc2) are the targets of hypothemycin or its downstream molecules in ubiquitin-conjugation process.	hypothemycin	15-27	ubiquitin conjugating enzyme E2 B	Homo sapiens	188-218
10421424-3	1999	Analysis using hypothemycin-resistant mutant of Schizosaccharomyces pombe (S. pombe) was carried out to show that S. pombe rhp6+ (homologue of Saccharomyces cerevisiae RAD6) and mammalian ubiquitin-conjugating enzyme 2 (ubc2) are the targets of hypothemycin or its downstream molecules in ubiquitin-conjugation process.	hypothemycin	15-27	ubiquitin conjugating enzyme E2 B	Homo sapiens	220-224
10421424-4	1999	Furthermore, in the presence of lactacystin, a specific inhibitor for proteasome, hypothemycin greatly enhanced the accumulation of multi-ubiquitinated form of cyclin D1 in DT cells.	hypothemycin	82-94	cyclin D1	Mus musculus	160-169
10421424-5	1999	Therefore, it is indicated that hypothemycin facilitates ubiquitinating process of cyclin D1.	hypothemycin	32-44	cyclin D1	Mus musculus	83-92
34150845-9	2021	The anticancer drug sensitivity analysis indicated that ZC3H13 expression had a positive relationship with anticancer drugs such as selumetinib, dabrafenib, cobimetinib, trametinib, and hypothemycin (p < 0.001).	hypothemycin	186-198	zinc finger CCCH-type containing 13	Homo sapiens	56-62