Target Information

Target General Infomation
Target ID
T60857
Former ID
TTDR00033
Target Name
Aldo-keto reductase family 1 member C3
Gene Name
AKR1C3
Synonyms
3-alpha-hydroxysteroid dehydrogenase; 3alpha-HSD; Chlordecone reductase homolog HAKRb; DD3; Dihydrodiol dehydrogenase 3; Dihydrodiol dehydrogenase, type I; HA1753; HPGFS; Human prostaglandin F synthase; Prostaglandin F synthase; Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; AKR1C3
Target Type
Successful
Disease Dysmenorrhea [ICD9: 625.3; ICD10: N94.4-N94.6]
Prostate cancer [ICD9: 185; ICD10: C61]
Function
Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (pg) d2, pgh2 and phenanthrenequinone (pq) and the oxidation of 9alpha,11beta- pgf2 to pgd2.
BioChemical Class
Short-chain dehydrogenases reductases
Target Validation
T60857
UniProt ID
P42330
EC Number
EC 1.3.1.20
Sequence
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPM
SLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKP
GLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLD
RNLHYFNSDSFASHPNYPYSDEY
Drugs and Mode of Action
Drug(s) Flufenamic Acid Drug Info Approved Dysmenorrhea [539575], [551871]
ASP-9521 Drug Info Phase 1/2 Prostate cancer [523469]
Inhibitor 2'-Monophosphoadenosine 5'-Diphosphoribose Drug Info [551393]
2,2-Dibenzylcyclopentanol Drug Info [529980]
2-(4-Chlorobenzylidene)cyclopentanone Drug Info [529980]
2-(4-chlorobenzylidene)cyclopentyl ethyl ether Drug Info [529980]
2-(4-chlorobenzylidene)cyclopentylmethyl ether Drug Info [529980]
2-Methyl-2,4-Pentanediol Drug Info [551393]
2-[(2,2-diphenylacetyl)amino]benzoic acid Drug Info [527759]
3-Bromo-5-phenylsalicylc acid Drug Info [530095]
3-Phenylcyclopentanecarboxylic acid Drug Info [529980]
4-ANDROSTENE-3-17-DIONE Drug Info [551374]
Acetate Ion Drug Info [551393]
EM-1424 Drug Info [528576]
EM1396 Drug Info [528576]
Flufenamic Acid Drug Info [551392]
M-Phenoxybenzoic Acid For Cis-Isomer Drug Info [527759]
Rutin Drug Info [551393]
Agonist 4-Androstenedione Drug Info [551393]
Modulator ASP-9521 Drug Info [532753], [532866]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway Superpathway of steroid hormone biosynthesis
Allopregnanolone biosynthesis
Androgen biosynthesis
KEGG Pathway Steroid hormone biosynthesis
Arachidonic acid metabolism
Metabolic pathways
Ovarian steroidogenesis
NetPath Pathway TGF_beta_Receptor Signaling Pathway
PathWhiz Pathway Arachidonic Acid Metabolism
Reactome Retinoid metabolism and transport
WikiPathways Metapathway biotransformation
Benzo(a)pyrene metabolism
Arachidonic acid metabolism
References
Ref 523469ClinicalTrials.gov (NCT01352208) Phase I/II Study of ASP9521 in Castrate-Resistant Prostate Cancer (CRPC) Patients. U.S. National Institutes of Health.
Ref 539575(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: 2447).
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 527759Bioorg Med Chem Lett. 2005 Dec 1;15(23):5170-5. Epub 2005 Sep 23.Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: new lead compounds for the development of anticancer agents.
Ref 528576J Biol Chem. 2007 Mar 16;282(11):8368-79. Epub 2006 Dec 13.Structure-based inhibitor design for an enzyme that binds different steroids: a potent inhibitor for human type 5 17beta-hydroxysteroid dehydrogenase.
Ref 529980Eur J Med Chem. 2009 Jun;44(6):2563-71. Epub 2009 Feb 5.New cyclopentane derivatives as inhibitors of steroid metabolizing enzymes AKR1C1 and AKR1C3.
Ref 530095J Med Chem. 2009 May 28;52(10):3259-64.Structure-guided design, synthesis, and evaluation of salicylic acid-based inhibitors targeting a selectivity pocket in the active site of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1).
Ref 532753Safety, tolerability and anti-tumour activity of the androgen biosynthesis inhibitor ASP9521 in patients with metastatic castration-resistant prostate cancer: multi-centre phase I/II study. Invest New Drugs. 2014 Oct;32(5):995-1004.
Ref 532866In vitro and in vivo characterisation of ASP9521: a novel, selective, orally bioavailable inhibitor of 17beta-hydroxysteroid dehydrogenase type 5 (17betaHSD5; AKR1C3). Invest New Drugs. 2014 Oct;32(5):860-70.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551392Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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