Details of the Drug Therapeutic Target (DTT)
General Information of Drug Therapeutic Target (DTT) (ID: TT5ZWB6)
DTT Name | Dihydrodiol dehydrogenase type I (AKR1C3) | ||||
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Synonyms |
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; Testosterone 17-beta-dehydrogenase 5; Prostaglandin F synthase; PGFS; KIAA0119; Indanol dehydrogenase; HSD17B5; HA1753; Dihydrodiol dehydrogenase 3; DDH1; DD3; DD-3; Chlordecone reductase homolog HAKRb; Aldo-keto reductase family 1 member C3; 3-alpha-hydroxysteroid dehydrogenase type 2; 3-alpha-HSD type II, brain; 3-alpha-HSD type 2; 17-beta-hydroxysteroid dehydrogenase type 5; 17-beta-HSD 5
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Gene Name | AKR1C3 | ||||
DTT Type |
Successful target
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BioChemical Class |
Short-chain dehydrogenases reductase
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UniProt ID | |||||
TTD ID | |||||
3D Structure | |||||
EC Number |
EC 1.-.-.-
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Sequence |
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPM SLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKP GLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPV LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLD RNLHYFNSDSFASHPNYPYSDEY |
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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 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
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KEGG Pathway | |||||
Reactome Pathway | |||||
BioCyc Pathway | |||||
Molecular Interaction Atlas (MIA) of This DTT
Molecular Interaction Atlas (MIA) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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1 Approved Drug(s) Targeting This DTT
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1 Clinical Trial Drug(s) Targeting This DTT
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13 Patented Agent(s) Targeting This DTT
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15 Investigative Drug(s) Targeting This DTT
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Molecular Expression Atlas (MEA) of This DTT
The Drug-Metabolizing Enzyme (DME) Role of This DTT
DTT DME Name | Aldo-keto reductase 1C3 (AKR1C3) | |||||||||||||||||||||||||||||||||||||||
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Gene Name | AKR1C3 | |||||||||||||||||||||||||||||||||||||||
2 Approved Drug(s) Metabolized by This DTT
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2 Clinical Trial Drug(s) Metabolized by This DTT
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3 Investigative Drug(s) Metabolized by This DTT
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References
1 | Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51. | ||||
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2 | 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. | ||||
3 | Aldo-Keto Reductase (AKR) 1C3 inhibitors: a patent review.Expert Opin Ther Pat. 2017 Dec;27(12):1329-1340. | ||||
4 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | ||||
5 | New cyclopentane derivatives as inhibitors of steroid metabolizing enzymes AKR1C1 and AKR1C3. Eur J Med Chem. 2009 Jun;44(6):2563-71. | ||||
6 | Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: new lead compounds for the development of ant... Bioorg Med Chem Lett. 2005 Dec 1;15(23):5170-5. | ||||
7 | Structure-guided design, synthesis, and evaluation of salicylic acid-based inhibitors targeting a selectivity pocket in the active site of human 20... J Med Chem. 2009 May 28;52(10):3259-64. | ||||
8 | Structure-based inhibitor design for an enzyme that binds different steroids: a potent inhibitor for human type 5 17beta-hydroxysteroid dehydrogenase. J Biol Chem. 2007 Mar 16;282(11):8368-79. | ||||
9 | Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3. Toxicol Lett. 2008 Sep;181(1):1-6. | ||||
10 | In vitro metabolism of fenofibric acid by carbonyl reducing enzymes. Chem Biol Interact. 2016 Oct 25;258:153-8. | ||||
11 | Expression and characterization of four recombinant human dihydrodiol dehydrogenase isoforms: oxidation of trans-7, 8-dihydroxy-7,8-dihydrobenzo[a]pyrene to the activated o-quinone metabolite benzo[a]pyrene-7,8-dione. Biochemistry. 1998 May 12;37(19):6781-90. | ||||
12 | The role of carbonyl reducing enzymes in oxcarbazepine in vitro metabolism in man. Chem Biol Interact. 2014 Sep 5;220:241-7. | ||||
13 | Instability of C154Y variant of aldo-keto reductase 1C3. Chem Biol Interact. 2017 Oct 1;276:194-202. | ||||