General Information of Drug Therapeutic Target (DTT) (ID: TT5ZWB6)

DTT Name Dihydrodiol dehydrogenase type I (AKR1C3)
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
Gene Name AKR1C3
DTT Type
Successful target
[1]
BioChemical Class
Short-chain dehydrogenases reductase
UniProt ID
AK1C3_HUMAN
TTD ID
T60857
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 1.-.-.-
Sequence
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPM
SLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKP
GLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLD
RNLHYFNSDSFASHPNYPYSDEY
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.
KEGG Pathway
Steroid hormone biosynthesis (hsa00140 )
Arachidonic acid metabolism (hsa00590 )
Metabolic pathways (hsa01100 )
Ovarian steroidogenesis (hsa04913 )
Reactome Pathway
Retinoid metabolism and transport (R-HSA-975634 )
BioCyc Pathway
MetaCyc:HS03054-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Flufenamic Acid DMC8VNH Dysmenorrhea GA34.3 Approved [1]
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1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
ASP-9521 DM8V0UL Prostate cancer 2C82.0 Phase 1/2 [2]
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13 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Beta-naphthylacetic acids derivative 1 DM5KTDY N. A. N. A. Patented [3]
Indomethacin analog 1 DM3E5V6 N. A. N. A. Patented [3]
Indomethacin analog 2 DMKFPJ7 N. A. N. A. Patented [3]
Indomethacin analog 3 DM53JXE N. A. N. A. Patented [3]
Isoquinolone derivative 1 DMW6R0H N. A. N. A. Patented [3]
N-(benzimidazole/indole) benzoic acid derivative 1 DMGQWKH N. A. N. A. Patented [3]
N-(benzimidazole/indole) benzoic acid derivative 2 DMOPUFM N. A. N. A. Patented [3]
N-(benzimidazolylcarbonyl)-piperidine derivative 1 DM541QW N. A. N. A. Patented [3]
N-(indolylcarbonyl)-piperidine derivative 1 DMARHJ9 N. A. N. A. Patented [3]
N-(naphthylamino)-benzoate derivative 1 DM310ES N. A. N. A. Patented [3]
N-(phenylamino)-benzoate derivative 1 DMNIWVG N. A. N. A. Patented [3]
N-(pyridinepyrroylylcarbonyl)-piperidine derivative 1 DMA85UD N. A. N. A. Patented [3]
Nitrogen/sulfur-substituted estrene derivative 1 DMD7OW0 N. A. N. A. Patented [3]
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⏷ Show the Full List of 13 Patented Agent(s)
15 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
2'-Monophosphoadenosine 5'-Diphosphoribose DME9S8M Discovery agent N.A. Investigative [4]
2,2-Dibenzylcyclopentanol DMFPYU8 Discovery agent N.A. Investigative [5]
2-(4-Chlorobenzylidene)cyclopentanone DMOH2YC Discovery agent N.A. Investigative [5]
2-(4-chlorobenzylidene)cyclopentyl ethyl ether DMFE93N Discovery agent N.A. Investigative [5]
2-(4-chlorobenzylidene)cyclopentylmethyl ether DMTW9B7 Discovery agent N.A. Investigative [5]
2-Methyl-2,4-Pentanediol DMD45CU Discovery agent N.A. Investigative [4]
2-[(2,2-diphenylacetyl)amino]benzoic acid DMVSTG7 Discovery agent N.A. Investigative [6]
3-Bromo-5-phenylsalicylc acid DMZTDCL Discovery agent N.A. Investigative [7]
3-Phenylcyclopentanecarboxylic acid DMJOD1T Discovery agent N.A. Investigative [5]
4-ANDROSTENE-3-17-DIONE DMSE8NU Discovery agent N.A. Investigative [4]
Acetate Ion DMD08RH Discovery agent N.A. Investigative [4]
EM-1424 DMSLHDN Discovery agent N.A. Investigative [8]
EM1396 DMZ2EL1 Discovery agent N.A. Investigative [8]
M-Phenoxybenzoic Acid For Cis-Isomer DMJRK47 Discovery agent N.A. Investigative [6]
Rutin DMEHRAJ Discovery agent N.A. Investigative [4]
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⏷ Show the Full List of 15 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Prostate cancer 2C82 Prostate 4.06E-01 1.39 0.74
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The Drug-Metabolizing Enzyme (DME) Role of This DTT

DTT DME Name Aldo-keto reductase 1C3 (AKR1C3) DME Info
Gene Name AKR1C3
2 Approved Drug(s) Metabolized by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [9]
FENOFIBRIC ACID DMGO2MC Cardiovascular disease BA00-BE2Z Approved [10]
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2 Clinical Trial Drug(s) Metabolized by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
ANDROSTERONE DMITJAK N. A. N. A. Phase 3 [11]
Trastuzumab emtansine DMU1LXS HER2-positive breast cancer 2C60-2C65 Phase 2 [12]
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3 Investigative Drug(s) Metabolized by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
4-oxo-nonenal DMPX1J9 Discovery agent N.A. Investigative [13]
Acenaphthenol DMT3QYZ N. A. N. A. Investigative [11]
Indan-1-ol DMMLQZJ N. A. N. A. Investigative [11]
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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.
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.