Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T60857
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| Former ID |
TTDR00033
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| Target Name |
Aldo-keto reductase family 1 member C3
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| Gene Name |
AKR1C3
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| 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
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| Target Type |
Successful
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| 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.
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| BioChemical Class |
Short-chain dehydrogenases reductases
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| Target Validation |
T60857
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| UniProt ID | |||||
| EC Number |
EC 1.3.1.20
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| Sequence |
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPM SLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKP GLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPV LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLD RNLHYFNSDSFASHPNYPYSDEY |
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| Drugs and Mode of Action | |||||
| Drug(s) | Flufenamic Acid | Drug Info | Approved | Dysmenorrhea | [1], [2] |
| ASP-9521 | Drug Info | Phase 1/2 | Prostate cancer | [3] | |
| Inhibitor | 2'-Monophosphoadenosine 5'-Diphosphoribose | Drug Info | [4] | ||
| 2,2-Dibenzylcyclopentanol | Drug Info | [5] | |||
| 2-(4-Chlorobenzylidene)cyclopentanone | Drug Info | [5] | |||
| 2-(4-chlorobenzylidene)cyclopentyl ethyl ether | Drug Info | [5] | |||
| 2-(4-chlorobenzylidene)cyclopentylmethyl ether | Drug Info | [5] | |||
| 2-Methyl-2,4-Pentanediol | Drug Info | [4] | |||
| 2-[(2,2-diphenylacetyl)amino]benzoic acid | Drug Info | [6] | |||
| 3-Bromo-5-phenylsalicylc acid | Drug Info | [7] | |||
| 3-Phenylcyclopentanecarboxylic acid | Drug Info | [5] | |||
| 4-ANDROSTENE-3-17-DIONE | Drug Info | [8] | |||
| Acetate Ion | Drug Info | [4] | |||
| EM-1424 | Drug Info | [9] | |||
| EM1396 | Drug Info | [9] | |||
| Flufenamic Acid | Drug Info | [10] | |||
| M-Phenoxybenzoic Acid For Cis-Isomer | Drug Info | [6] | |||
| Rutin | Drug Info | [4] | |||
| Agonist | 4-Androstenedione | Drug Info | [4] | ||
| Modulator | ASP-9521 | Drug Info | [11], [12] | ||
| 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 1 | (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 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | ||||
| REF 3 | ClinicalTrials.gov (NCT01352208) Phase I/II Study of ASP9521 in Castrate-Resistant Prostate Cancer (CRPC) Patients. U.S. National Institutes of Health. | ||||
| REF 4 | How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | ||||
| REF 5 | Eur 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 6 | Bioorg 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 7 | J 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 8 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | ||||
| REF 9 | J 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 10 | Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51. | ||||
| REF 11 | Safety, 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 12 | In 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. | ||||
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