PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
6196675-10	1983	E2 and 4-OHE2 competed for binding to AFP to an approximately equal extent.	4-ohe2	7-13	alpha-fetoprotein	Rattus norvegicus	38-41
31147316-17	2019	NC preferentially inhibited the nontoxic E2 2-hydroxylation pathway mediated by CYP1A1, which might increase the risk of 4-OHE2-induced genotoxicity and cause severe drug-drug interactions.	4-ohe2	121-127	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	80-86
31493422-1	2019	Cytochrome P450 1B1 (CYP1B1) is a key enzyme that catalyzes the metabolism of 17beta-estradiol (E2) into catechol estrogens, such as 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2).	4-ohe2	185-191	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	0-19
31493422-1	2019	Cytochrome P450 1B1 (CYP1B1) is a key enzyme that catalyzes the metabolism of 17beta-estradiol (E2) into catechol estrogens, such as 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2).	4-ohe2	185-191	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	21-27
31493422-7	2019	Treatment with 4-OHE2, mainly formed by CYP1B1 activity, also increased XIAP protein levels, whereas treatment with 2-OHE2 did not have a significant effect.	4-ohe2	15-21	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	40-46
31493422-7	2019	Treatment with 4-OHE2, mainly formed by CYP1B1 activity, also increased XIAP protein levels, whereas treatment with 2-OHE2 did not have a significant effect.	4-ohe2	15-21	X-linked inhibitor of apoptosis	Homo sapiens	72-76
31493422-8	2019	Treatment with 4-OHE2 significantly prevented proteasome-mediated XIAP degradation.	4-ohe2	15-21	X-linked inhibitor of apoptosis	Homo sapiens	66-70
31493422-9	2019	In addition, phosphorylation of XIAP on serine 87, which is known to stabilize XIAP, was up-regulated by 4-OHE2, indicating that 4-OHE2 affects XIAP stability through XIAP phosphorylation.	4-ohe2	105-111	X-linked inhibitor of apoptosis	Homo sapiens	32-36
31493422-9	2019	In addition, phosphorylation of XIAP on serine 87, which is known to stabilize XIAP, was up-regulated by 4-OHE2, indicating that 4-OHE2 affects XIAP stability through XIAP phosphorylation.	4-ohe2	105-111	X-linked inhibitor of apoptosis	Homo sapiens	79-83
31493422-9	2019	In addition, phosphorylation of XIAP on serine 87, which is known to stabilize XIAP, was up-regulated by 4-OHE2, indicating that 4-OHE2 affects XIAP stability through XIAP phosphorylation.	4-ohe2	105-111	X-linked inhibitor of apoptosis	Homo sapiens	79-83
31493422-9	2019	In addition, phosphorylation of XIAP on serine 87, which is known to stabilize XIAP, was up-regulated by 4-OHE2, indicating that 4-OHE2 affects XIAP stability through XIAP phosphorylation.	4-ohe2	105-111	X-linked inhibitor of apoptosis	Homo sapiens	79-83
31493422-9	2019	In addition, phosphorylation of XIAP on serine 87, which is known to stabilize XIAP, was up-regulated by 4-OHE2, indicating that 4-OHE2 affects XIAP stability through XIAP phosphorylation.	4-ohe2	129-135	X-linked inhibitor of apoptosis	Homo sapiens	32-36
31493422-9	2019	In addition, phosphorylation of XIAP on serine 87, which is known to stabilize XIAP, was up-regulated by 4-OHE2, indicating that 4-OHE2 affects XIAP stability through XIAP phosphorylation.	4-ohe2	129-135	X-linked inhibitor of apoptosis	Homo sapiens	79-83
31493422-9	2019	In addition, phosphorylation of XIAP on serine 87, which is known to stabilize XIAP, was up-regulated by 4-OHE2, indicating that 4-OHE2 affects XIAP stability through XIAP phosphorylation.	4-ohe2	129-135	X-linked inhibitor of apoptosis	Homo sapiens	79-83
31493422-9	2019	In addition, phosphorylation of XIAP on serine 87, which is known to stabilize XIAP, was up-regulated by 4-OHE2, indicating that 4-OHE2 affects XIAP stability through XIAP phosphorylation.	4-ohe2	129-135	X-linked inhibitor of apoptosis	Homo sapiens	79-83
31493422-10	2019	We also found that phosphorylation of protein kinase C (PKC)epsilon, which is required for XIAP phosphorylation, increased when cells were treated with 4-OHE2.	4-ohe2	152-158	protein kinase C epsilon	Homo sapiens	56-67
31493422-10	2019	We also found that phosphorylation of protein kinase C (PKC)epsilon, which is required for XIAP phosphorylation, increased when cells were treated with 4-OHE2.	4-ohe2	152-158	X-linked inhibitor of apoptosis	Homo sapiens	91-95
28119082-2	2017	17beta-Estradiol (E2) is hydrolyzed to 4-hydroxy-E2 (4-OHE2) via cytochrome P450 (CYP) 1B1 in vivo.	4-ohe2	53-59	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	65-90
30680817-7	2019	In conclusion, this study demonstrated that oroxylin A showed a stronger inhibitory effect than baicalein on CYP1B1-mediated 4-OHE2 formation in MCF-7 cells, providing crucial implications for their possibly preventive/therapeutic potential against breast cancer via inhibition of CYP1B1, particularly of oroxylin A.	4-ohe2	125-131	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	109-115
30680817-1	2019	Human cytochrome P450 1B1 (CYP1B1)-mediated formation of 4-hydroxyestradiol (4-OHE2) from 17beta-estradiol plays an important role in the progression of human breast cancer, while the biotransformation of 17beta-estradiol to 2-hydroxyestradiol mediated by cytochrome P450 1A1 (CYP1A1) is considered as a less harmful pathway.	4-ohe2	77-83	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	6-25
30680817-1	2019	Human cytochrome P450 1B1 (CYP1B1)-mediated formation of 4-hydroxyestradiol (4-OHE2) from 17beta-estradiol plays an important role in the progression of human breast cancer, while the biotransformation of 17beta-estradiol to 2-hydroxyestradiol mediated by cytochrome P450 1A1 (CYP1A1) is considered as a less harmful pathway.	4-ohe2	77-83	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	27-33
30680817-1	2019	Human cytochrome P450 1B1 (CYP1B1)-mediated formation of 4-hydroxyestradiol (4-OHE2) from 17beta-estradiol plays an important role in the progression of human breast cancer, while the biotransformation of 17beta-estradiol to 2-hydroxyestradiol mediated by cytochrome P450 1A1 (CYP1A1) is considered as a less harmful pathway.	4-ohe2	77-83	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	256-275
30680817-1	2019	Human cytochrome P450 1B1 (CYP1B1)-mediated formation of 4-hydroxyestradiol (4-OHE2) from 17beta-estradiol plays an important role in the progression of human breast cancer, while the biotransformation of 17beta-estradiol to 2-hydroxyestradiol mediated by cytochrome P450 1A1 (CYP1A1) is considered as a less harmful pathway.	4-ohe2	77-83	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	277-283
28119082-9	2017	Taken together the data suggested that fisetin is able to inhibit the formation of carcinogenic 4-OHE2 from E2, which reveals one of its anti-cancer mechanisms and helps to reveal the relationship between the structure of flavonoids and the inhibition CYP1B1 for discovering new drugs in cancer therapy and prevention.	4-ohe2	96-102	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	252-258
23685341-3	2013	Exposure to 2-OHE2, 4-OHE2 or E2 resulted in a significant increase in the protein abundance of cyclin D1 and c-myc.	4-ohe2	20-26	cyclin D1	Homo sapiens	96-105
23685341-3	2013	Exposure to 2-OHE2, 4-OHE2 or E2 resulted in a significant increase in the protein abundance of cyclin D1 and c-myc.	4-ohe2	20-26	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	110-115
23685341-5	2013	BPH-1 cells treated with 4-OHE2 showed increased abundance of estrogen receptor-alpha (ERalpha) and its downstream IGF-1R.	4-ohe2	25-31	estrogen receptor 1	Homo sapiens	62-85
23685341-5	2013	BPH-1 cells treated with 4-OHE2 showed increased abundance of estrogen receptor-alpha (ERalpha) and its downstream IGF-1R.	4-ohe2	25-31	estrogen receptor 1	Homo sapiens	87-94
23685341-5	2013	BPH-1 cells treated with 4-OHE2 showed increased abundance of estrogen receptor-alpha (ERalpha) and its downstream IGF-1R.	4-ohe2	25-31	insulin like growth factor 1 receptor	Homo sapiens	115-121
23448447-4	2013	Among them, CYP1B1 predominantly catalyzes the C4-position of E2 and forms carcinogenic 4-hydroxy-E2 (4-OHE2), whereas CYP1A1 and CYP1A2 convert E2 to noncarcinogenic 2-hydroxy-E2.	4-ohe2	102-108	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	12-18
23448447-4	2013	Among them, CYP1B1 predominantly catalyzes the C4-position of E2 and forms carcinogenic 4-hydroxy-E2 (4-OHE2), whereas CYP1A1 and CYP1A2 convert E2 to noncarcinogenic 2-hydroxy-E2.	4-ohe2	102-108	cystatin 12, pseudogene	Homo sapiens	62-100
21170676-1	2011	Extensive data suggest that estradiol contributes to the development of breast cancer by acting as a mitogen and exerting direct genotoxic effects after enzymatic conversion to 4-hydroxyestradiol (4-OHE2) via cytochrome P450 1B1 (CYP1B1).	4-ohe2	197-203	cytochrome P450, family 1, subfamily b, polypeptide 1	Mus musculus	209-228
21170676-1	2011	Extensive data suggest that estradiol contributes to the development of breast cancer by acting as a mitogen and exerting direct genotoxic effects after enzymatic conversion to 4-hydroxyestradiol (4-OHE2) via cytochrome P450 1B1 (CYP1B1).	4-ohe2	197-203	cytochrome P450, family 1, subfamily b, polypeptide 1	Mus musculus	230-236
16893557-4	2006	For rat CYP1B1, the apparent Km values for the formation of 4-OHE2 and 2-OHE2 were 0.61+/-0.23 and 1.84+/-0.73 microM; the turnover numbers (Kcat) were 0.23+/-0.02 and 0.46+/-0.05 pmol/min/pmol P450; and the catalytic efficiencies (Kcat/Km) were 0.37 and 0.25, respectively.	4-ohe2	60-66	cytochrome P450, family 1, subfamily b, polypeptide 1	Rattus norvegicus	8-14
16893557-5	2006	For human CYP1B1, the apparent Km values for the formation of 4-OHE2 and 2-OHE2 were 1.22+/-0.25 and 1.10+/-0.26; the turnover numbers were 1.23+/-0.06 and 0.33+/-0.02; and the catalytic efficiencies were 1.0 and 0.30, respectively.	4-ohe2	62-68	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	10-16
16411670-5	2006	In similar experiments, the relative reactivity of 4-OHE2 and 2-OHE2 with DNA was determined after activation by lactoperoxidase, tyrosinase, prostaglandin H synthase (PHS), or 3-methylcholanthrene-induced rat liver microsomes.	4-ohe2	51-57	tyrosinase	Rattus norvegicus	130-140
16411670-7	2006	Similar results were obtained with lactoperoxidase or tyrosinase-catalyzed oxidation of 4-OHE2 and 2-OHE2, whereas with activation by PHS or microsomes, a relatively higher amount of the depurinating adduct from E2-2,3-Q was detected.	4-ohe2	88-94	tyrosinase	Rattus norvegicus	54-64
15050414-5	2004	Estradiol (E2) is usually metabolized by CYP1A1/1A2 and CYP3A4 to the 2-hydroxy estradiol (2-OHE2) and 4-hydroxy estradiol (4-OHE2) in human liver.	4-ohe2	124-130	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	41-47
15050414-5	2004	Estradiol (E2) is usually metabolized by CYP1A1/1A2 and CYP3A4 to the 2-hydroxy estradiol (2-OHE2) and 4-hydroxy estradiol (4-OHE2) in human liver.	4-ohe2	124-130	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	56-62
15050414-8	2004	In the present study, we have demonstrated that one of the catechol estrogen metabolites of E2, 4-OHE2, induces HIF-1alpha and VEGF-A expression at protein level in two human ovarian cancer cell lines, OVCAR-3 and A2780-CP70 cells, in dose- and time-dependent manners, whereas the other catechol estrogen metabolite of E2, 2-OHE2, does not alter HIF-1alpha and VEGF-A expression.	4-ohe2	96-102	hypoxia inducible factor 1 subunit alpha	Homo sapiens	112-122
15050414-8	2004	In the present study, we have demonstrated that one of the catechol estrogen metabolites of E2, 4-OHE2, induces HIF-1alpha and VEGF-A expression at protein level in two human ovarian cancer cell lines, OVCAR-3 and A2780-CP70 cells, in dose- and time-dependent manners, whereas the other catechol estrogen metabolite of E2, 2-OHE2, does not alter HIF-1alpha and VEGF-A expression.	4-ohe2	96-102	vascular endothelial growth factor A	Homo sapiens	127-133
15050414-8	2004	In the present study, we have demonstrated that one of the catechol estrogen metabolites of E2, 4-OHE2, induces HIF-1alpha and VEGF-A expression at protein level in two human ovarian cancer cell lines, OVCAR-3 and A2780-CP70 cells, in dose- and time-dependent manners, whereas the other catechol estrogen metabolite of E2, 2-OHE2, does not alter HIF-1alpha and VEGF-A expression.	4-ohe2	96-102	hypoxia inducible factor 1 subunit alpha	Homo sapiens	346-356
15050414-8	2004	In the present study, we have demonstrated that one of the catechol estrogen metabolites of E2, 4-OHE2, induces HIF-1alpha and VEGF-A expression at protein level in two human ovarian cancer cell lines, OVCAR-3 and A2780-CP70 cells, in dose- and time-dependent manners, whereas the other catechol estrogen metabolite of E2, 2-OHE2, does not alter HIF-1alpha and VEGF-A expression.	4-ohe2	96-102	vascular endothelial growth factor A	Homo sapiens	361-367
15050414-9	2004	To explore the mechanism of 4-OHE2-induced HIF-1alpha and VEGF-A expression, we studied whether phosphatidylinositol 3-kinase (PI3K) or mitogen-activated protein kinase (MAPK) signaling pathways are involved in 4-OHE2-induced HIF-1alpha and VEGF-A expression.	4-ohe2	28-34	hypoxia inducible factor 1 subunit alpha	Homo sapiens	43-53
15050414-9	2004	To explore the mechanism of 4-OHE2-induced HIF-1alpha and VEGF-A expression, we studied whether phosphatidylinositol 3-kinase (PI3K) or mitogen-activated protein kinase (MAPK) signaling pathways are involved in 4-OHE2-induced HIF-1alpha and VEGF-A expression.	4-ohe2	28-34	vascular endothelial growth factor A	Homo sapiens	58-64
12376470-2	2002	The two major pathways of estrogen metabolism, to the carcinogenic 4-hydroxyestradiol (4-OHE2) and to the non-carcinogenic 2-hydroxyestradiol (2-OHE2), are mediated by cytochromes P450 CYP1B1 and CYP1A1, respectively.	4-ohe2	87-93	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	185-191
12376470-2	2002	The two major pathways of estrogen metabolism, to the carcinogenic 4-hydroxyestradiol (4-OHE2) and to the non-carcinogenic 2-hydroxyestradiol (2-OHE2), are mediated by cytochromes P450 CYP1B1 and CYP1A1, respectively.	4-ohe2	87-93	cytochrome P450 family 1 subfamily A member 1	Homo sapiens	196-202
23685341-6	2013	Reduced abundance of estrogen receptor-beta (ERbeta) and its downstream tumor suppressor FOXO-1 were observed in cells exposed to E2, 2-OHE2 and, to a greater extent, 4-OHE2.	4-ohe2	167-173	estrogen receptor 2	Homo sapiens	21-43
23685341-6	2013	Reduced abundance of estrogen receptor-beta (ERbeta) and its downstream tumor suppressor FOXO-1 were observed in cells exposed to E2, 2-OHE2 and, to a greater extent, 4-OHE2.	4-ohe2	167-173	estrogen receptor 2	Homo sapiens	45-51
23685341-6	2013	Reduced abundance of estrogen receptor-beta (ERbeta) and its downstream tumor suppressor FOXO-1 were observed in cells exposed to E2, 2-OHE2 and, to a greater extent, 4-OHE2.	4-ohe2	167-173	forkhead box O1	Homo sapiens	89-95
16893557-1	2006	Previous work demonstrated that human cytochrome P4501B1 (CYP1B1) forms predominantly 4-hydroxyestradiol (4-OHE2), a metabolite which is carcinogenic in animal models.	4-ohe2	106-112	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	38-56
16893557-1	2006	Previous work demonstrated that human cytochrome P4501B1 (CYP1B1) forms predominantly 4-hydroxyestradiol (4-OHE2), a metabolite which is carcinogenic in animal models.	4-ohe2	106-112	cytochrome P450 family 1 subfamily B member 1	Homo sapiens	58-64
16893557-2	2006	Here, we present results from kinetic studies characterizing the formation of 4-OHE2 and 2-hydroxyestradiol (2-OHE2) by rat CYP1B1 using 17beta-estradiol (E2) as a substrate.	4-ohe2	78-84	cytochrome P450, family 1, subfamily b, polypeptide 1	Rattus norvegicus	124-130
16287077-9	2006	Cells treated with E2 or 4-OHE2 at doses of 0.007 nM and 70 nM and 2-OHE2 only at a higher dose (3.6 microM) exhibited a 5 bp deletion in p53 exon 4.	4-ohe2	25-31	tumor protein p53	Homo sapiens	138-141
15050414-11	2004	4-OHE2, but not 2-OHE2, also induced Akt phosphorylation at Ser473 in dose- and time-dependent manners, and LY294002 and wortmannin inhibited Akt phosphorylation at Ser473 induced by 4-OHE2.	4-ohe2	0-6	AKT serine/threonine kinase 1	Homo sapiens	37-40
15050414-11	2004	4-OHE2, but not 2-OHE2, also induced Akt phosphorylation at Ser473 in dose- and time-dependent manners, and LY294002 and wortmannin inhibited Akt phosphorylation at Ser473 induced by 4-OHE2.	4-ohe2	0-6	AKT serine/threonine kinase 1	Homo sapiens	142-145
15050414-12	2004	Our results also indicated that the mTOR/FRAP inhibitor, rapamycin, inhibited 4-OHE2-induced HIF-1alpha and VEGF-A expression.	4-ohe2	78-84	mechanistic target of rapamycin kinase	Homo sapiens	36-40
15050414-12	2004	Our results also indicated that the mTOR/FRAP inhibitor, rapamycin, inhibited 4-OHE2-induced HIF-1alpha and VEGF-A expression.	4-ohe2	78-84	mechanistic target of rapamycin kinase	Homo sapiens	41-45
15050414-12	2004	Our results also indicated that the mTOR/FRAP inhibitor, rapamycin, inhibited 4-OHE2-induced HIF-1alpha and VEGF-A expression.	4-ohe2	78-84	hypoxia inducible factor 1 subunit alpha	Homo sapiens	93-103
15050414-12	2004	Our results also indicated that the mTOR/FRAP inhibitor, rapamycin, inhibited 4-OHE2-induced HIF-1alpha and VEGF-A expression.	4-ohe2	78-84	vascular endothelial growth factor A	Homo sapiens	108-114
15050414-13	2004	These results suggest that the PI3K/Akt/FRAP signaling pathway is required for HIF-1alpha and VEGF-A expression induced by 4-OHE2, whereas the MAPK pathway is not required.	4-ohe2	123-129	AKT serine/threonine kinase 1	Homo sapiens	36-39
15050414-13	2004	These results suggest that the PI3K/Akt/FRAP signaling pathway is required for HIF-1alpha and VEGF-A expression induced by 4-OHE2, whereas the MAPK pathway is not required.	4-ohe2	123-129	mechanistic target of rapamycin kinase	Homo sapiens	40-44
15050414-13	2004	These results suggest that the PI3K/Akt/FRAP signaling pathway is required for HIF-1alpha and VEGF-A expression induced by 4-OHE2, whereas the MAPK pathway is not required.	4-ohe2	123-129	hypoxia inducible factor 1 subunit alpha	Homo sapiens	79-89
15050414-13	2004	These results suggest that the PI3K/Akt/FRAP signaling pathway is required for HIF-1alpha and VEGF-A expression induced by 4-OHE2, whereas the MAPK pathway is not required.	4-ohe2	123-129	vascular endothelial growth factor A	Homo sapiens	94-100
15050414-14	2004	The finding that induction of HIF-1alpha and VEGF-A expression occurs via the activation of the PI3K/Akt/FRAP signaling pathway could be an important mechanism of 4-OHE2-induced carcinogenesis.	4-ohe2	163-169	hypoxia inducible factor 1 subunit alpha	Homo sapiens	30-40
15050414-14	2004	The finding that induction of HIF-1alpha and VEGF-A expression occurs via the activation of the PI3K/Akt/FRAP signaling pathway could be an important mechanism of 4-OHE2-induced carcinogenesis.	4-ohe2	163-169	vascular endothelial growth factor A	Homo sapiens	45-51
15050414-14	2004	The finding that induction of HIF-1alpha and VEGF-A expression occurs via the activation of the PI3K/Akt/FRAP signaling pathway could be an important mechanism of 4-OHE2-induced carcinogenesis.	4-ohe2	163-169	AKT serine/threonine kinase 1	Homo sapiens	101-104
15050414-14	2004	The finding that induction of HIF-1alpha and VEGF-A expression occurs via the activation of the PI3K/Akt/FRAP signaling pathway could be an important mechanism of 4-OHE2-induced carcinogenesis.	4-ohe2	163-169	mechanistic target of rapamycin kinase	Homo sapiens	105-109
11906176-7	2002	SULT1E1 had the lowest apparent K(m) values, 0.31, 0.18, 0.27, and 0.22 microM for 4-OHE1, 4-OHE2, 2-OHE1, and 2-OHE2, respectively.	4-ohe2	91-97	sulfotransferase family 1E member 1	Homo sapiens	0-7