Target Information

Target General Infomation
Target ID
T84621
Former ID
TTDS00420
Target Name
Cytochrome P450 11B1, mitochondrial
Gene Name
CYP11B1
Synonyms
CYPXIB1; P-450c11; P450C11; S11BH; Steroid 11-beta-hydroxylase; CYP11B1
Target Type
Successful
Disease Breast cancer [ICD9: 174, 175; ICD10: C50]
Cushing's disease [ICD9: 255; ICD10: E24.0]
Congestive heart failure; Myocardial fibrosis; Hyperaldosteronism [ICD9: 255.1, 425.0, 425.3, 428, 428.0, 709.2; ICD10: E26, I42.0, I42.5, I50, L90.5]
Function
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB.
BioChemical Class
Oxidoreductases acting on paired donors
Target Validation
T84621
UniProt ID
P15538
EC Number
EC 1.14.15.4
Sequence
MALRAKAEVCMAVPWLSLQRAQALGTRAARVPRTVLPFEAMPRRPGNRWLRLLQIWREQG
YEDLHLEVHQTFQELGPIFRYDLGGAGMVCVMLPEDVEKLQQVDSLHPHRMSLEPWVAYR
QHRGHKCGVFLLNGPEWRFNRLRLNPEVLSPNAVQRFLPMVDAVARDFSQALKKKVLQNA
RGSLTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQLMFM
PRSLSRWTSPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFSRPQQYTSIVAELLLNAELS
PDAIKANSMELTAGSVDTTVFPLLMTLFELARNPNVQQALRQESLAAAASISEHPQKATT
ELPLLRAALKETLRLYPVGLFLERVASSDLVLQNYHIPAGTLVRVFLYSLGRNPALFPRP
ERYNPQRWLDIRGSGRNFYHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHLQVETLTQED
IKMVYSFILRPSMFPLLTFRAIN
Drugs and Mode of Action
Drug(s) FADROZOLE Drug Info Approved Breast cancer [543063], [544743], [551871]
Metyrapone Drug Info Approved Cushing's disease [468277], [538462]
Inhibitor (3-((1H-imidazol-1-yl)methyl)phenyl)methanol Drug Info [530679]
(4-((1H-imidazol-1-yl)methyl)phenyl)methanol Drug Info [530679]
1-(2-Phenoxy-ethyl)-1H-imidazole Drug Info [533496]
1-(3,4-dihydronaphthalen-2-yl)-1H-imidazole Drug Info [528109]
1-(3-Bromobenzyl)-1H-imidazole Drug Info [530679]
1-(3-Chlorobenzyl)-1H-imidazole Drug Info [530679]
1-(3-Fluorobenzyl)-1H-imidazole Drug Info [530679]
1-(3-Methoxy-naphthalen-2-yl)-1H-imidazole Drug Info [527801]
1-(4-Aminobenzyl)-1H-imidazole Drug Info [530679]
1-(4-Bromobenzyl)-1H-imidazole Drug Info [530679]
1-(4-Bromobenzyl)-5-phenyl-1H-imidazole Drug Info [530679]
1-(4-Chlorobenzyl)-5-phenyl-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-(2-fluorophenyl)-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-(2-methylphenyl)-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-(3-fluorophenyl)-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-(3-methylphenyl)-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-(4-fluorophenyl)-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-(4-methylphenyl)-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-(4-pyridyl)-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-bromo-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-formyl-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-hydroxymethyl-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-methyl-1H-imidazole Drug Info [530679]
1-(4-Cyanobenzyl)-5-phenyl-1H-imidazole Drug Info [530679]
1-(4-fluorobenzyl)-1H-imidazole Drug Info [530679]
1-(4-Fluorobenzyl)-5-phenyl-1H-imidazole Drug Info [530679]
1-(4-Methoxybenzyl)-5-phenyl-1H-imidazole Drug Info [530679]
1-(6-Methoxy-naphthalen-2-yl)-1H-imidazole Drug Info [527801]
1-Benzyl-5-phenyl-1H-imidazole Drug Info [530679]
1-Ethyl-3-imidazol-1-ylmethyl-1H-indole Drug Info [533418]
1-Naphthalen-2-yl-1H-imidazole Drug Info [527801]
1-Phenyl-2-pyridin-3-yl-propan-1-one Drug Info [533562]
2-Methyl-1,2-di-pyridin-3-yl-1-methoxypropane Drug Info [533562]
2-Methyl-1,2-di-pyridin-3-yl-propan-1-one oxime Drug Info [533562]
2-Methyl-1,2-di-pyridin-3-yl-propane Drug Info [533562]
2-Methyl-1,2-di-pyridin-3-yl-propylchloride Drug Info [533562]
2-Methyl-1,2-di-pyridin-3-yl-propyliodide Drug Info [533562]
2-Methyl-1-phenyl-2-pyridin-3-yl-propan-1-ol Drug Info [533562]
2-Methyl-1-phenyl-2-pyridin-3-yl-propan-1-one Drug Info [533562]
3-((1H-imidazol-1-yl)methyl)aniline Drug Info [530679]
3-(1,1-Dimethyl-2-phenyl-ethyl)-pyridine Drug Info [533562]
3-(1,2-dihydroacenaphthylen-3-yl)pyridine Drug Info [527819]
3-(1,2-dihydroacenaphthylen-5-yl)pyridine Drug Info [527819]
3-(1-Benzyl-1H-imidazol-5-yl)-1-propanol Drug Info [530679]
3-(1-Chloro-7-methoxy-naphthalen-2-yl)-pyridine Drug Info [527801]
3-(1-ethyl-3,4-dihydronaphthalen-2-yl)-pyridine Drug Info [528109]
3-(1-methyl-3,4-dihydronaphthalen-2-yl)-pyridine Drug Info [528109]
3-(1H-inden-2-yl)pyridine Drug Info [528109]
3-(2,3-Dihydro-1,4-benzodioxin-6-yl)pyridine Drug Info [529834]
3-(2-Chloro-1,1-dimethyl-2-phenyl-ethyl)-pyridine Drug Info [533562]
3-(3,4-dihydronaphthalen-2-yl)pyridine Drug Info [528109]
3-(3-Benzyl-6-methoxynaphthalen-2-yl)pyridine Drug Info [529667]
3-(3-Benzylnaphthalen-2-yl)pyridine Drug Info [529667]
3-(3-methyl-3,4-dihydronaphthalen-2-yl)pyridine Drug Info [528109]
3-(4-ethyl-3,4-dihydronaphthalen-2-yl)pyridine Drug Info [528109]
3-(4-methyl-3,4-dihydronaphthalen-2-yl)pyridine Drug Info [528109]
3-(5,6,7,8-Tetrahydronaphthalen-2-yl)pyridine Drug Info [529834]
3-(5-Bromo-6-methoxy-naphthalen-2-yl)-pyridine Drug Info [527801]
3-(5-Chloro-6-methoxy-naphthalen-2-yl)-pyridine Drug Info [527801]
3-(5-methoxy-1H-inden-2-yl)pyridine Drug Info [528109]
3-(6-Bromo-naphthalen-2-yl)-pyridine Drug Info [527801]
3-(6-Ethoxy-naphthalen-2-yl)-pyridine Drug Info [527801]
3-(6-methoxy-3,4-dihydronaphthalen-2-yl)pyridine Drug Info [529624]
3-(6-Methoxy-3-methylnaphthalen-2-yl)pyridine Drug Info [529624]
3-(6-Methoxynaphthalen-2-yl)-4-methylpyridine Drug Info [529624]
3-(6-Methoxynaphthalen-2-yl)-5-phenylpyridine Drug Info [529624]
3-(6-Methoxynaphthalen-2-yl)pyridin-4-amine Drug Info [529624]
3-(6-methoxynaphthalen-2-yl)pyridine Drug Info [529667]
3-(naphthalen-2-yl)pyridine Drug Info [529667]
3-Ethoxy-5-(6-methoxynaphthalen-2-yl)pyridine Drug Info [529624]
3-Fluoro-4'-(pyridin-4-ylmethyl)biphenyl-4-ol Drug Info [531085]
3-Imidazol-1-yl-quinoline Drug Info [527801]
3-Imidazol-1-ylmethyl-1H-indole Drug Info [533418]
3-Imidazol-1-ylmethyl-2-isopropyl-1H-indole Drug Info [533418]
3-Indan-(1E)-ylidenemethyl-pyridine Drug Info [527456]
3-Indan-(1Z)-ylidenemethyl-pyridine Drug Info [527456]
3-MeSO2-DDE Drug Info [535383]
3-methoxy-5-(6-methoxynaphthalen-2-yl)pyridine Drug Info [529624]
3-Phenanthren-9-yl-pyridine Drug Info [527801]
3-[(Z)-2-phenylvinyl]pyridine Drug Info [528109]
3-[1-(4-Bromobenzyl)-1H-imidazol-5-yl]-1-propanol Drug Info [530679]
3-[1-(4-Cyanobenzyl)-1H-imidazol-5-yl]-1-propanol Drug Info [530679]
3-[3-(4-Methoxybenzyl)naphthalen-2-yl]pyridine Drug Info [529667]
3-[4-Chloro-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
3-[4-Chloro-indan-(1Z)-ylidenemethyl]-pyridine Drug Info [527456]
3-[4-Fluoro-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
3-[4-Methyl-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
3-[5-Bromo-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
3-[5-Bromo-indan-(1Z)-ylidenemethyl]-pyridine Drug Info [527456]
3-[5-Chloro-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
3-[5-Chloro-indan-(1Z)-ylidenemethyl]-pyridine Drug Info [527456]
3-[5-Ethoxy-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
3-[5-Ethoxy-indan-(1Z)-ylidenemethyl]-pyridine Drug Info [527456]
3-[5-Fluoro-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
3-[5-Fluoro-indan-(1Z)-ylidenemethyl]-pyridine Drug Info [527456]
3-[5-Methoxy-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
3-[5-Methoxy-indan-(1Z)-ylidenemethyl]-pyridine Drug Info [527456]
3-[7-Methoxy-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
4'-(Pyridin-4-ylmethyl)biphenyl-3,4-diamine Drug Info [531085]
4'-(Pyridin-4-ylmethyl)biphenyl-3,4-diol Drug Info [531085]
4'-(Pyridin-4-ylmethyl)biphenyl-3-amine Drug Info [531085]
4'-(Pyridin-4-ylmethyl)biphenyl-4-amine Drug Info [531085]
4-((1H-imidazol-1-yl)methyl)benzonitrile Drug Info [530679]
4-((3',4'-Difluorobiphenyl-4-yl)methyl)pyridine Drug Info [531085]
4-(2-Imidazol-1-yl-ethoxy)-benzamide Drug Info [533496]
4-(4'-Fluoro-biphenyl-4-ylmethyl)pyridine Drug Info [531085]
4-(4-(thiophen-2-yl)benzyl)pyridine Drug Info [531085]
4-(4-(thiophen-3-yl)benzyl)pyridine Drug Info [531085]
4-(6-methoxy-3,4-dihydronaphthalen-2-yl)pyridine Drug Info [528109]
4-(6-Methoxy-3-methylnaphthalen-2-yl)isoquinoline Drug Info [529624]
4-(6-Methoxynaphthalen-2-yl)isoquinoline Drug Info [529624]
4-Indan-(1Z)-ylidenemethyl-pyridine Drug Info [527456]
4-[(3'-Hydroxybiphenyl-4-yl)methyl]pyridine Drug Info [531085]
4-[(4'-Hydroxybiphenyl-4-yl)methyl]pyridine Drug Info [531085]
4-[5-Bromo-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
4-[5-Bromo-indan-(1Z)-ylidenemethyl]-pyridine Drug Info [527456]
4-[5-Chloro-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
4-[5-Chloro-indan-(1Z)-ylidenemethyl]-pyridine Drug Info [527456]
4-[5-Fluoro-indan-(1E)-ylidenemethyl]-pyridine Drug Info [527456]
4-[5-Fluoro-indan-(1Z)-ylidenemethyl]-pyridine Drug Info [527456]
5-(6-Methoxynaphthalen-2-yl)pyridin-3-ol Drug Info [529624]
5-Indan-(1E)-ylidenemethyl-1H-imidazole Drug Info [527475]
5-Indan-(1Z)-ylidenemethyl-1H-imidazole Drug Info [527475]
5-Naphthalen-2-yl-1H-imidazole Drug Info [527801]
5-Naphthalen-2-yl-oxazole Drug Info [527801]
5-Pyridin-3-yl-1,3-dihydro-2H-indol-2-one Drug Info [529834]
5-Pyridin-3-yl-2,3-dihydro-1H-inden-1-one Drug Info [529834]
5-[4-(Pyridin-4-ylmethyl)phenyl]-1H-indole Drug Info [531085]
5-[5-Bromo-indan-(1E)-ylidenemethyl]-1H-imidazole Drug Info [527475]
5-[5-Bromo-indan-(1Z)-ylidenemethyl]-1H-imidazole Drug Info [527475]
5-[5-Fluoro-indan-(1E)-ylidenemethyl]-pyrimidine Drug Info [527456]
6-(4-Methylpyridin-3-yl)-2-naphthonitrile Drug Info [529624]
6-(pyridin-3-yl)-2-naphthonitrile Drug Info [529624]
6-Isoquinolin-4-yl-3,4-dihydroquinolin-2(1H)-one Drug Info [529834]
6-Pyridin-3-yl-1,2,3,4-tetrahydronaphthalen-2-ol Drug Info [529834]
6-Pyridin-3-yl-3,4-dihydro-1H-quinolin-2-one Drug Info [529834]
6-Pyridin-3-yl-3,4-dihydronaphthalen-2(1H)-one Drug Info [529834]
6-Pyridin-3-yl-3,4-dihydroquinoline-2(1H)-thione Drug Info [529834]
6-Pyridin-3-yl-naphthalen-2-ol Drug Info [527801]
6-[4-(Pyridin-4-ylmethyl)phenyl]naphthalen-2-ol Drug Info [531085]
7-(1-(1H-imidazol-1-yl)ethyl)-9H-fluoren-2-ol Drug Info [529625]
7-Pyridin-3-yl-2H-1,4-benzothiazin-3(4H)-one Drug Info [529834]
BENZYLIMIDAZOLE Drug Info [530679]
FADROZOLE Drug Info [530679]
Methyl 3-(1-Benzyl-1H-imidazol-5-yl)-propanoate Drug Info [530679]
METYRAPOL Drug Info [533562]
Metyrapone Drug Info [535383]
N-(4'-Isonicotinoylbiphenyl-3-yl)acetamide Drug Info [531085]
R-fadrozole Drug Info [530679]
SL125 Drug Info [551088]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway Superpathway of steroid hormone biosynthesis
Glucocorticoid biosynthesis
Mineralocorticoid biosynthesis
KEGG Pathway Steroid hormone biosynthesis
Metabolic pathways
PathWhiz Pathway Steroidogenesis
Reactome Glucocorticoid biosynthesis
Endogenous sterols
WikiPathways Metapathway biotransformation
Oxidation by Cytochrome P450
Metabolism of steroid hormones and vitamin D
Corticotropin-releasing hormone
References
Ref 468277(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5224).
Ref 538462FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 012911.
Ref 543063(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8311).
Ref 544743Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000824)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 527456J Med Chem. 2005 Mar 10;48(5):1563-75.Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitors of aldosterone synthase.
Ref 527475J Med Chem. 2005 Mar 24;48(6):1796-805.Synthesis and evaluation of imidazolylmethylenetetrahydronaphthalenes and imidazolylmethyleneindanes: potent inhibitors of aldosterone synthase.
Ref 527801J Med Chem. 2005 Oct 20;48(21):6632-42.Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis.
Ref 527819Bioorg Med Chem Lett. 2006 Jan 1;16(1):25-30. Epub 2005 Oct 21.Development and evaluation of a pharmacophore model for inhibitors of aldosterone synthase (CYP11B2).
Ref 528109J Med Chem. 2006 Apr 6;49(7):2222-31.Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis.
Ref 529624J Med Chem. 2008 Aug 28;51(16):5064-74. Epub 2008 Aug 1.Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: influence of heteroaryl derivatization onpotency and selectivity.
Ref 529625Bioorg Med Chem. 2008 Aug 15;16(16):7715-27. Epub 2008 Jul 9.Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17)--part II: Core rigidification and influence of substituents at the methylene bridge.
Ref 529667J Med Chem. 2008 Oct 9;51(19):6138-49. Epub 2008 Sep 3.Novel aldosterone synthase inhibitors with extended carbocyclic skeleton by a combined ligand-based and structure-based drug design approach.
Ref 529834J Med Chem. 2008 Dec 25;51(24):8077-87.In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-1H-quinolin-2-one derivatives.
Ref 530679J Med Chem. 2010 Feb 25;53(4):1712-25.Synthesis, biological evaluation, and molecular modeling of 1-benzyl-1H-imidazoles as selective inhibitors of aldosterone synthase (CYP11B2).
Ref 531085J Med Chem. 2010 Aug 12;53(15):5749-58.Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer.
Ref 533418J Med Chem. 1986 Mar;29(3):342-6.Selective thromboxane synthetase inhibitors. 2. 3-(1H-imidazol-1-ylmethyl)-2-methyl-1H-indole-1-propanoic acid and analogues.
Ref 533496J Med Chem. 1985 Oct;28(10):1427-32.Selective thromboxane synthetase inhibitors. 1. 1-[(Aryloxy)alkyl]-1H-imidazoles.
Ref 533562J Med Chem. 1984 Jan;27(1):15-9.Structure-activity relationship study of the inhibition of adrenal cortical 11 beta-hydroxylase by new metyrapone analogues.
Ref 535383Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line. Toxicol In Vitro. 2002 Apr;16(2):113-21.
Ref 551088Reduction of cell proliferation induced by PD166866: an inhibitor of the basic fibroblast growth factor. J Exp Clin Cancer Res. 2007 Sep;26(3):405-9.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.