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
• 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

2 Approved Drug(s) Metabolized by This DME

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]

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	[11]
Trastuzumab emtansine	DMU1LXS	HER2-positive breast cancer	2C60-2C65	Phase 2	[12]

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	[13]
Acenaphthenol	DMT3QYZ	N. A.	N. A.	Investigative	[11]
Indan-1-ol	DMMLQZJ	N. A.	N. A.	Investigative	[11]

Experimental Enzyme Kinetic Data of Drugs

Drug Name	Indication	Highest Status	Kinetic Data	REF
ANDROSTERONE	N. A.	Phase 3	Km = 0.0035 microM	[11]

Molecular Expression Atlas (MEA) 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

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]

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]

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]

References

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