Target General Infomation
Target ID
T92521
Former ID
TTDR00242
Target Name
Cytochrome P450 1B1
Gene Name
CYP1B1
Synonyms
CYPIB1; CYP1B1
Target Type
Clinical Trial
Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids,fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta- estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.
BioChemical Class
Oxidoreductases acting on paired donors
Target Validation
T92521
UniProt ID
EC Number
EC 1.14.14.1
Sequence
MGTSLSPNDPWPLNPLSIQQTTLLLLLSVLATVHVGQRLLRQRRRQLRSAPPGPFAWPLI
GNAAAVGQAAHLSFARLARRYGDVFQIRLGSCPIVVLNGERAIHQALVQQGSAFADRPAF
ASFRVVSGGRSMAFGHYSEHWKVQRRAAHSMMRNFFTRQPRSRQVLEGHVLSEARELVAL
LVRGSADGAFLDPRPLTVVAVANVMSAVCFGCRYSHDDPEFRELLSHNEEFGRTVGAGSL
VDVMPWLQYFPNPVRTVFREFEQLNRNFSNFILDKFLRHCESLRPGAAPRDMMDAFILSA
EKKAAGDSHGGGARLDLENVPATITDIFGASQDTLSTALQWLLLLFTRYPDVQTRVQAEL
DQVVGRDRLPCMGDQPNLPYVLAFLYEAMRFSSFVPVTIPHATTANTSVLGYHIPKDTVV
FVNQWSVNHDPLKWPNPENFDPARFLDKDGLINKDLTSRVMIFSVGKRRCIGEELSKMQL
FLFISILAHQCDFRANPNEPAKMNFSYGLTIKPKSFKVNVTLRESMELLDSAVQNLQAKE
TCQ
Drugs and Mode of Action
Drug(s) PINOCEMBRIN Drug Info Phase 2 Discovery agent [524643]
NARINGENIN Drug Info Phase 1 Discovery agent [522980]
Inhibitor 2-[2-(3,5-Dimethoxy-phenyl)-vinyl]-thiophene Drug Info [526231]
3-[2-(3,5-Dimethoxy-phenyl)-vinyl]-furan Drug Info [526231]
4-[2-(3,5-Dimethoxy-phenyl)-vinyl]-pyridine Drug Info [526231]
ACACETIN Drug Info [531094]
APIGENIN Drug Info [531094]
CHRYSIN Drug Info [531094]
CHRYSOERIOL Drug Info [531094]
DIOSMETIN Drug Info [531094]
ERIODICTYOL Drug Info [531094]
GALANGIN Drug Info [531094]
HOMOERIODICTYOL Drug Info [531094]
ISORHAMNETIN Drug Info [531094]
ISOSAKUTANETIN Drug Info [531094]
KAEMPFERIDE Drug Info [531094]
KAEMPFEROL Drug Info [531094]
N-(2,4-Dimethoxy-phenyl)-3,5-dimethoxy-benzamide Drug Info [526231]
NARINGENIN Drug Info [531094]
PINOCEMBRIN Drug Info [531094]
TAMARIXETIN Drug Info [531094]
TRISMETHOXYRESVERATROL Drug Info [526231]
Pathways
BioCyc Pathway Superpathway of tryptophan utilization
Superpathway of melatonin degradation
Melatonin degradation I
KEGG Pathway Steroid hormone biosynthesis
Tryptophan metabolism
Metabolism of xenobiotics by cytochrome P450
Ovarian steroidogenesis
Chemical carcinogenesis
MicroRNAs in cancer
NetPath Pathway TSH Signaling Pathway
IL4 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
Reactome Endogenous sterols
WikiPathways Metapathway biotransformation
Estrogen metabolism
Benzo(a)pyrene metabolism
Tamoxifen metabolism
Tryptophan metabolism
Oxidation by Cytochrome P450
Nuclear Receptors Meta-Pathway
Estrogen Receptor Pathway
Sulindac Metabolic Pathway
Arylhydrocarbon receptor (AhR) signaling pathway
miR-targeted genes in muscle cell - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in epithelium - TarBase
miR-targeted genes in adipocytes - TarBase
Phase 1 - Functionalization of compounds
References
Ref 522980ClinicalTrials.gov (NCT01091077) A Pilot Study of the Grapefruit Flavonoid Naringenin for HCV Infection. U.S. National Institutes of Health.
Ref 524643ClinicalTrials.gov (NCT02059785) Phase ???tudy of Pinocembrin Injection to Treat Ischemic Stroke. U.S. National Institutes of Health.
Ref 526231J Med Chem. 2002 Jan 3;45(1):160-4.Design, synthesis, and discovery of novel trans-stilbene analogues as potent and selective human cytochrome P450 1B1 inhibitors.
Ref 531094Bioorg Med Chem. 2010 Sep 1;18(17):6310-5. Epub 2010 Jul 13.Selective inhibition of methoxyflavonoids on human CYP1B1 activity.

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