Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEGQTXO)

DME Name Aldo-keto reductase 1C3 (AKR1C3)
Synonyms
Aldo-keto reductase family 1 member C3; Chlordecone reductase homolog HAKRb; DD-3; DD3; Dihydrodiol dehydrogenase 3; Dihydrodiol dehydrogenase type I; HA1753; HSD17B5; KIAA0119; PGFS; Prostaglandin F synthase; Testosterone 17-beta-dehydrogenase 5; 17-beta-HSD 5; 17-beta-hydroxysteroid dehydrogenase type 5; 3-alpha-HSD type 2; 3-alpha-HSD type II, brain; 3-alpha-hydroxysteroid dehydrogenase type 2; AKR1C3
Gene Name AKR1C3
UniProt ID
AK1C3_HUMAN
INTEDE ID
DME0118
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
8644
EC Number EC: 1.1.1.357
Oxidoreductase
CH-OH donor oxidoreductase
NAD/NADP oxidoreductase
EC: 1.1.1.357
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPM
SLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKP
GLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLD
RNLHYFNSDSFASHPNYPYSDEY
Function
This enzyme catalyzes the conversion of aldehydes and ketones to alcohols. It catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2 and functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Besides, it can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites and preferentially transforms androstenedione (4-dione) to testosterone.
KEGG Pathway
Arachidonic acid metabolism (hsa00590 )
Folate biosynthesis (hsa00790 )
Metabolic pathways (hsa01100 )
Ovarian steroidogenesis (hsa04913 )
Steroid hormone biosynthesis (hsa00140 )
Reactome Pathway
Retinoid metabolism and transport (R-HSA-975634 )
Synthesis of Prostaglandins (PG) and Thromboxanes (TX) (R-HSA-2162123 )
Synthesis of bile acids and bile salts via 24-hydroxycholesterol (R-HSA-193775 )
Synthesis of bile acids and bile salts via 27-hydroxycholesterol (R-HSA-193807 )
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol (R-HSA-193368 )
RA biosynthesis pathway (R-HSA-5365859 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
2 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Solid tumour/cancer 2A00-2F9Z Approved [11]
Fenofibric acid DMGO2MC Cardiovascular disease BA00-BE2Z Approved [12]
2 Clinical Trial Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Androsterone DMITJAK N. A. N. A. Phase 3 [13]
Trastuzumab Emtansine DMU1LXS HER2-positive breast cancer 2C60-2C65 Phase 2 [14]
3 Investigative Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
4-oxo-nonenal DMPX1J9 Discovery agent N.A. Investigative [15]
Acenaphthenol DMT3QYZ Discovery agent N.A. Investigative [13]
Indan-1-ol DMMLQZJ Discovery agent N.A. Investigative [13]
Experimental Enzyme Kinetic Data of Drugs
Drug Name Indication Highest Status Kinetic Data REF
Androsterone N. A. Phase 3 Km = 0.0035 microM [13]

Molecular Expression Atlas (MEA) of This DME

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DME
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 4.82E-04 1.84E-02 2.12E-02
Alopecia ED70 Skin from scalp 3.71E-06 4.70E-01 1.11E+00
Alzheimer's disease 8A20 Entorhinal cortex 7.33E-09 6.56E-01 9.55E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 2.22E-01 1.12E+00 1.44E+00
Aortic stenosis BB70 Calcified aortic valve 3.97E-01 -4.06E-01 -2.92E-01
Apnea 7A40 Hyperplastic tonsil 1.04E-02 -1.83E+00 -1.36E+00
Arthropathy FA00-FA5Z Peripheral blood 4.02E-01 -7.63E-02 -1.01E-01
Asthma CA23 Nasal and bronchial airway 4.95E-07 9.04E-01 9.14E-01
Atopic dermatitis EA80 Skin 2.44E-06 -7.99E-01 -1.60E+00
Autism 6A02 Whole blood 9.70E-01 1.25E-01 1.19E-01
Autoimmune uveitis 9A96 Peripheral monocyte 3.05E-03 -4.36E-01 -7.29E-01
Autosomal dominant monocytopenia 4B04 Whole blood 3.12E-04 2.13E+00 3.83E+00
Bacterial infection of gingival 1C1H Gingival tissue 6.86E-03 -2.22E-01 -3.84E-01
Batten disease 5C56.1 Whole blood 5.20E-01 -4.39E-02 -5.58E-02
Behcet's disease 4A62 Peripheral blood 3.39E-01 2.34E-02 3.57E-02
Bipolar disorder 6A60-6A6Z Prefrontal cortex 9.37E-01 1.93E-02 5.33E-02
Bladder cancer 2C94 Bladder tissue 4.11E-07 -1.83E+00 -3.22E+00
Breast cancer 2C60-2C6Z Breast tissue 5.64E-91 -3.30E+00 -2.02E+00
Cardioembolic stroke 8B11.20 Whole blood 1.42E-03 -4.58E-01 -9.87E-01
Cervical cancer 2C77 Cervical tissue 6.55E-02 -4.21E-01 -3.88E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 3.81E-01 -6.64E-01 -3.95E-01
Chronic hepatitis C 1E51.1 Whole blood 1.24E-01 -2.60E-01 -2.76E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 5.02E-01 -1.50E-01 -2.45E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 3.90E-07 9.07E-01 9.64E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 2.47E-01 -6.06E-01 -1.40E+00
Colon cancer 2B90 Colon tissue 3.63E-76 -1.23E+00 -2.11E+00
Coronary artery disease BA80-BA8Z Peripheral blood 1.22E-01 2.47E+00 1.39E+00
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 6.97E-01 9.38E-02 1.73E-01
Endometriosis GA10 Endometrium tissue 6.38E-03 -7.94E-01 -7.17E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 8.19E-02 -2.65E-01 -3.12E-01
Familial hypercholesterolemia 5C80.00 Whole blood 9.40E-02 -1.27E-01 -1.72E-01
Gastric cancer 2B72 Gastric tissue 6.74E-01 -1.38E+00 -6.11E-01
Glioblastopma 2A00.00 Nervous tissue 2.33E-07 3.68E-01 4.16E-01
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 8.79E-01 1.49E-01 1.57E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 7.00E-03 1.68E+00 1.29E+00
Head and neck cancer 2D42 Head and neck tissue 3.19E-02 -7.72E-01 -5.54E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 4.30E-01 -2.09E-01 -2.29E-01
Huntington's disease 8A01.10 Whole blood 7.12E-02 7.10E-01 1.22E+00
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 7.96E-02 -3.20E-01 -4.51E-01
Immunodeficiency 4A00-4A20 Peripheral blood 1.63E-02 7.01E-01 8.53E-01
Influenza 1E30 Whole blood 6.50E-01 4.08E-01 5.24E-01
Interstitial cystitis GC00.3 Bladder tissue 3.46E-06 -2.34E+00 -6.20E+00
Intracranial aneurysm 8B01.0 Intracranial artery 5.79E-01 8.20E-02 2.83E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 1.81E-03 -3.54E-01 -7.55E-01
Ischemic stroke 8B11 Peripheral blood 7.16E-01 -1.20E-01 -1.06E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 2.63E-06 -5.07E-01 -6.93E-01
Lateral sclerosis 8B60.4 Skin 5.58E-01 1.92E-01 2.12E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 2.08E-01 -2.14E-01 -6.01E-01
Liver cancer 2C12.0 Liver tissue 2.66E-10 1.14E+00 1.76E+00
Liver failure DB99.7-DB99.8 Liver tissue 1.78E-01 -1.08E+00 -1.60E+00
Lung cancer 2C25 Lung tissue 7.96E-02 -9.31E-03 -1.64E-02
Lupus erythematosus 4A40 Whole blood 8.95E-01 2.20E-01 1.29E-01
Major depressive disorder 6A70-6A7Z Hippocampus 2.24E-01 -2.11E-01 -5.69E-01
Major depressive disorder 6A70-6A7Z Whole blood 7.88E-02 -3.37E-01 -3.41E-01
Melanoma 2C30 Skin 3.42E-05 -2.19E+00 -1.22E+00
Multiple myeloma 2A83.1 Peripheral blood 9.72E-01 -2.20E-02 -1.63E-02
Multiple myeloma 2A83.1 Bone marrow 1.78E-01 -1.90E-01 -5.12E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 4.91E-02 -6.04E-01 -1.02E+00
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 1.30E-02 1.05E-01 2.06E-01
Myelofibrosis 2A20.2 Whole blood 3.85E-01 3.96E-01 5.43E-01
Myocardial infarction BA41-BA50 Peripheral blood 6.29E-01 1.74E-01 1.38E-01
Myopathy 8C70.6 Muscle tissue 3.52E-04 1.51E+00 2.13E+00
Neonatal sepsis KA60 Whole blood 3.17E-09 -1.04E+00 -1.02E+00
Neuroectodermal tumour 2A00.11 Brain stem tissue 5.30E-03 -1.20E+00 -1.58E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 5.18E-01 4.94E-01 6.99E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 2.45E-02 5.01E-01 1.17E+00
Olive pollen allergy CA08.00 Peripheral blood 1.67E-01 -7.22E-01 -1.13E+00
Oral cancer 2B6E Oral tissue 7.81E-03 8.71E-01 5.33E-01
Osteoarthritis FA00-FA0Z Synovial tissue 3.30E-01 9.01E-02 1.11E-01
Osteoporosis FB83.1 Bone marrow 6.26E-03 -1.29E+00 -2.15E+00
Ovarian cancer 2C73 Ovarian tissue 5.28E-01 -9.15E-01 -5.67E-01
Pancreatic cancer 2C10 Pancreas 5.05E-04 1.52E+00 1.19E+00
Parkinson's disease 8A00.0 Substantia nigra tissue 6.15E-03 1.20E+00 1.54E+00
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 2.77E-01 -4.87E-01 -6.71E-01
Pituitary cancer 2D12 Pituitary tissue 5.67E-04 -1.57E+00 -1.99E+00
Pituitary gonadotrope tumour 2D12 Pituitary tissue 3.84E-05 -1.85E+00 -3.14E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 3.13E-01 -4.34E-01 -5.41E-01
Polycythemia vera 2A20.4 Whole blood 1.15E-02 -1.55E-01 -2.02E-01
Pompe disease 5C51.3 Biceps muscle 4.19E-08 2.17E+00 4.61E+00
Preterm birth KA21.4Z Myometrium 2.69E-01 4.48E-01 7.17E-01
Prostate cancer 2C82 Prostate 4.06E-01 1.39E+00 7.42E-01
Psoriasis EA90 Skin 7.43E-09 -5.23E-01 -8.41E-01
Rectal cancer 2B92 Rectal colon tissue 6.84E-09 -1.19E+00 -5.08E+00
Renal cancer 2C90-2C91 Kidney 4.73E-01 8.04E-01 5.39E-01
Retinoblastoma 2D02.2 Uvea 4.40E-06 -4.32E+00 -1.06E+01
Rheumatoid arthritis FA20 Synovial tissue 4.08E-03 5.34E-01 9.42E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 1.61E-01 3.15E-02 9.70E-02
Schizophrenia 6A20 Prefrontal cortex 8.46E-01 3.02E-01 2.43E-01
Schizophrenia 6A20 Superior temporal cortex 3.66E-01 -2.00E-02 -3.63E-02
Scleroderma 4A42.Z Whole blood 3.52E-01 -9.13E-02 -9.89E-02
Seizure 8A60-8A6Z Whole blood 1.54E-01 2.30E-01 2.93E-01
Sensitive skin EK0Z Skin 3.00E-01 -2.12E-01 -4.49E+00
Sepsis with septic shock 1G41 Whole blood 2.09E-23 -1.21E+00 -1.33E+00
Shwachman-Diamond syndrome 3A70.0 Bone marrow 1.67E-01 -1.36E-01 -3.15E-01
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 2.41E-01 -1.43E-01 -1.67E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 7.52E-01 7.87E-02 2.09E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 6.21E-03 5.87E-01 4.93E+00
Skin cancer 2C30-2C3Z Skin 1.01E-110 -2.94E+00 -4.04E+00
Thrombocythemia 3B63 Whole blood 2.37E-01 -1.22E-01 -1.68E-01
Thrombocytopenia 3B64 Whole blood 5.68E-01 7.35E-01 6.54E-01
Thyroid cancer 2D10 Thyroid 2.37E-21 -1.19E+00 -2.28E+00
Tibial muscular dystrophy 8C75 Muscle tissue 2.98E-01 -2.27E-01 -1.80E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 1.84E-01 3.35E-01 1.12E+00
Type 2 diabetes 5A11 Liver tissue 8.18E-01 -9.35E-02 -3.45E-01
Ureter cancer 2C92 Urothelium 1.36E-01 8.68E-02 1.29E-01
Uterine cancer 2C78 Endometrium tissue 1.33E-01 2.94E-01 2.30E-01
Vitiligo ED63.0 Skin 9.98E-01 3.55E-02 1.54E-01
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⏷ Show the Full List of DME Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name Dihydrodiol dehydrogenase type I (AKR1C3) DTT Info
DME DTT Type Successful
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]
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], [3]
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 [4]
Indomethacin analog 1 DM3E5V6 N. A. N. A. Patented [4]
Indomethacin analog 2 DMKFPJ7 N. A. N. A. Patented [4]
Indomethacin analog 3 DM53JXE N. A. N. A. Patented [4]
Isoquinolone derivative 1 DMW6R0H N. A. N. A. Patented [4]
N-(benzimidazole/indole) benzoic acid derivative 1 DMGQWKH N. A. N. A. Patented [4]
N-(benzimidazole/indole) benzoic acid derivative 2 DMOPUFM N. A. N. A. Patented [4]
N-(benzimidazolylcarbonyl)-piperidine derivative 1 DM541QW N. A. N. A. Patented [4]
N-(indolylcarbonyl)-piperidine derivative 1 DMARHJ9 N. A. N. A. Patented [4]
N-(naphthylamino)-benzoate derivative 1 DM310ES N. A. N. A. Patented [4]
N-(phenylamino)-benzoate derivative 1 DMNIWVG N. A. N. A. Patented [4]
N-(pyridinepyrroylylcarbonyl)-piperidine derivative 1 DMA85UD N. A. N. A. Patented [4]
Nitrogen/sulfur-substituted estrene derivative 1 DMD7OW0 N. A. N. A. Patented [4]
⏷ 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 [5]
2,2-Dibenzylcyclopentanol DMFPYU8 Discovery agent N.A. Investigative [6]
2-(4-Chlorobenzylidene)cyclopentanone DMOH2YC Discovery agent N.A. Investigative [6]
2-(4-chlorobenzylidene)cyclopentyl ethyl ether DMFE93N Discovery agent N.A. Investigative [6]
2-(4-chlorobenzylidene)cyclopentylmethyl ether DMTW9B7 Discovery agent N.A. Investigative [6]
2-Methyl-2,4-Pentanediol DMD45CU Discovery agent N.A. Investigative [5]
2-[(2,2-diphenylacetyl)amino]benzoic acid DMVSTG7 Discovery agent N.A. Investigative [7]
3-Bromo-5-phenylsalicylc acid DMZTDCL Discovery agent N.A. Investigative [8]
3-Phenylcyclopentanecarboxylic acid DMJOD1T Discovery agent N.A. Investigative [6]
4-ANDROSTENE-3-17-DIONE DMSE8NU Discovery agent N.A. Investigative [5], [9]
Acetate Ion DMD08RH Discovery agent N.A. Investigative [5]
EM-1424 DMSLHDN Discovery agent N.A. Investigative [10]
EM1396 DMZ2EL1 Discovery agent N.A. Investigative [10]
M-Phenoxybenzoic Acid For Cis-Isomer DMJRK47 Discovery agent N.A. Investigative [7]
Rutin DMEHRAJ Discovery agent N.A. Investigative [5]
⏷ Show the Full List of 15 Investigative Drug(s)

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 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.
4 Aldo-Keto Reductase (AKR) 1C3 inhibitors: a patent review.Expert Opin Ther Pat. 2017 Dec;27(12):1329-1340.
5 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
6 New cyclopentane derivatives as inhibitors of steroid metabolizing enzymes AKR1C1 and AKR1C3. Eur J Med Chem. 2009 Jun;44(6):2563-71.
7 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.
8 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.
9 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
10 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.
11 Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3. Toxicol Lett. 2008 Sep;181(1):1-6.
12 In vitro metabolism of fenofibric acid by carbonyl reducing enzymes. Chem Biol Interact. 2016 Oct 25;258:153-8.
13 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.
14 The role of carbonyl reducing enzymes in oxcarbazepine in vitro metabolism in man. Chem Biol Interact. 2014 Sep 5;220:241-7.
15 Instability of C154Y variant of aldo-keto reductase 1C3. Chem Biol Interact. 2017 Oct 1;276:194-202.