Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DE3N2FM)

• DME Name: NADPH-cytochrome P450 reductase (CPR)
• Synonyms: NADPH--cytochrome P450 reductase; P450R; CPR; CYPOR; POR
• Gene Name: POR
• UniProt ID: NCPR_HUMAN
• INTEDE ID: DME0076
• Gene ID: 5447
• EC Number:
  EC: 1.6.2.4
  Oxidoreductase
  NADH/NADPH oxidoreductase
  Heme protein acceptor oxidoreductase
  EC: 1.6.2.4
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MGDSHVDTSSTVSEAVAEEVSLFSMTDMILFSLIVGLLTYWFLFRKKKEEVPEFTKIQTL
  TSSVRESSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMSADPEEYDLA
  DLSSLPEIDNALVVFCMATYGEGDPTDNAQDFYDWLQETDVDLSGVKFAVFGLGNKTYEH
  FNAMGKYVDKRLEQLGAQRIFELGLGDDDGNLEEDFITWREQFWPAVCEHFGVEATGEES
  SIRQYELVVHTDIDAAKVYMGEMGRLKSYENQKPPFDAKNPFLAAVTTNRKLNQGTERHL
  MHLELDISDSKIRYESGDHVAVYPANDSALVNQLGKILGADLDVVMSLNNLDEESNKKHP
  FPCPTSYRTALTYYLDITNPPRTNVLYELAQYASEPSEQELLRKMASSSGEGKELYLSWV
  VEARRHILAILQDCPSLRPPIDHLCELLPRLQARYYSIASSSKVHPNSVHICAVVVEYET
  KAGRINKGVATNWLRAKEPAGENGGRALVPMFVRKSQFRLPFKATTPVIMVGPGTGVAPF
  IGFIQERAWLRQQGKEVGETLLYYGCRRSDEDYLYREELAQFHRDGALTQLNVAFSREQS
  HKVYVQHLLKQDREHLWKLIEGGAHIYVCGDARNMARDVQNTFYDIVAELGAMEHAQAVD
  YIKKLMTKGRYSLDVWS
• Function: This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes and can also provide electron transfer to heme oxygenase and cytochrome B5.
• Reactome Pathway: Cytochrome P450 - arranged by substrate type (R-HSA-211897)

Molecular Interaction Atlas (MIA) of This DME

7 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Benzphetamine	DMIJATC	Obesity	5B81	Approved	[3]
Daunorubicin	DMQUSBT	Acute myeloid leukaemia	2A60	Approved	[4]
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Menadiol sodium diphosphate	DMP9N85	Coagulation defect	3B10.0	Approved	[6]
Nilutamide	DMFN07X	Prostate cancer	2C82.0	Approved	[7]
Nitrofurantoin	DM7PQIK	Urinary tract infection	GC08	Approved	[8]
Tacrolimus	DMZ7XNQ	Organ transplant rejection	NE84	Approved	[9]

1 Clinical Trial Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amrubicin	DM6SGUB	Small-cell lung cancer	2C25.Y	Phase 3	[10]

1 Investigative Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitrobenzodiazepine	DM254EW	Discovery agent	N.A.	Investigative	[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	5.32E-02	-9.38E-02	-2.04E-01
Alopecia	ED70	Skin from scalp	3.70E-01	-2.11E-02	-5.57E-02
Alzheimer's disease	8A20	Entorhinal cortex	2.17E-05	-8.88E-02	-4.14E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	2.28E-01	1.02E-01	3.28E-01
Aortic stenosis	BB70	Calcified aortic valve	7.42E-01	2.12E-01	2.03E-01
Apnea	7A40	Hyperplastic tonsil	7.17E-01	3.96E-01	1.32E+00
Arthropathy	FA00-FA5Z	Peripheral blood	1.07E-01	2.52E-01	1.03E+00
Asthma	CA23	Nasal and bronchial airway	8.05E-01	4.10E-02	2.98E-02
Atopic dermatitis	EA80	Skin	4.68E-02	1.15E-01	1.69E-01
Autism	6A02	Whole blood	1.36E-01	7.56E-02	2.61E-01
Autoimmune uveitis	9A96	Peripheral monocyte	6.18E-01	-1.95E-01	-7.86E-01
Autosomal dominant monocytopenia	4B04	Whole blood	7.57E-01	-5.22E-03	-1.27E-02
Bacterial infection of gingival	1C1H	Gingival tissue	7.06E-02	-8.87E-02	-2.47E-01
Batten disease	5C56.1	Whole blood	8.89E-01	-4.49E-02	-3.72E-01
Behcet's disease	4A62	Peripheral blood	8.07E-01	9.66E-02	2.86E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	9.30E-01	-6.03E-02	-3.72E-01
Bladder cancer	2C94	Bladder tissue	6.72E-01	-2.29E-02	-6.05E-02
Breast cancer	2C60-2C6Z	Breast tissue	6.22E-08	2.88E-01	4.56E-01
Cardioembolic stroke	8B11.20	Whole blood	8.38E-02	1.31E-01	5.63E-01
Cervical cancer	2C77	Cervical tissue	3.21E-01	-1.19E-01	-1.51E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	8.92E-01	-1.61E-01	-1.97E-01
Chronic hepatitis C	1E51.1	Whole blood	4.72E-01	-8.18E-02	-3.04E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	5.51E-02	-1.59E-01	-3.33E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	1.83E-01	-1.94E-02	-4.08E-02
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	2.39E-01	-7.56E-01	-7.25E-01
Colon cancer	2B90	Colon tissue	2.27E-01	-1.01E-01	-2.46E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	9.08E-01	-6.21E-02	-3.00E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	3.89E-01	1.92E-01	5.90E-01
Endometriosis	GA10	Endometrium tissue	2.98E-04	3.72E-01	1.30E+00
Familial hypercholesterolemia	5C80.00	Peripheral blood	5.50E-01	3.56E-03	1.54E-02
Familial hypercholesterolemia	5C80.00	Whole blood	1.74E-12	9.19E-01	2.61E+00
Gastric cancer	2B72	Gastric tissue	4.09E-02	5.57E-01	2.14E+00
Glioblastopma	2A00.00	Nervous tissue	1.84E-16	1.43E-01	3.93E-01
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	9.44E-02	-2.62E-01	-2.29E+00
Glioma	2A00.0Y-2A00.0Z	White matter tissue	1.88E-04	4.24E-01	1.58E+00
Head and neck cancer	2D42	Head and neck tissue	1.95E-13	-5.94E-01	-5.63E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	9.12E-01	-7.51E-02	-1.99E-01
Huntington's disease	8A01.10	Whole blood	2.47E-01	7.05E-02	1.35E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	6.36E-01	5.41E-02	1.69E-01
Immunodeficiency	4A00-4A20	Peripheral blood	4.37E-02	-1.27E-01	-9.34E-01
Influenza	1E30	Whole blood	2.61E-02	-6.72E-01	-3.47E+00
Interstitial cystitis	GC00.3	Bladder tissue	1.17E-01	-4.00E-01	-8.20E-01
Intracranial aneurysm	8B01.0	Intracranial artery	4.01E-02	4.74E-01	1.07E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	1.07E-01	-2.07E-01	-5.36E-01
Ischemic stroke	8B11	Peripheral blood	6.70E-01	1.26E-01	6.00E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	3.86E-01	-1.08E-01	-2.58E-01
Lateral sclerosis	8B60.4	Skin	6.49E-01	3.90E-02	6.06E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	8.56E-02	-1.91E-01	-6.63E-01
Liver cancer	2C12.0	Liver tissue	1.09E-01	-2.00E-01	-3.21E-01
Liver failure	DB99.7-DB99.8	Liver tissue	1.39E-02	-1.25E+00	-2.00E+00
Lung cancer	2C25	Lung tissue	2.67E-37	-4.65E-01	-1.27E+00
Lupus erythematosus	4A40	Whole blood	1.92E-02	-2.76E-01	-4.16E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	6.16E-01	-5.51E-03	-3.56E-02
Major depressive disorder	6A70-6A7Z	Whole blood	1.01E-01	1.73E-02	4.17E-02
Melanoma	2C30	Skin	9.89E-01	-2.29E-01	-2.43E-01
Multiple myeloma	2A83.1	Peripheral blood	1.52E-02	-3.51E-01	-1.75E+00
Multiple myeloma	2A83.1	Bone marrow	7.25E-03	5.48E-01	1.55E+00
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	5.72E-01	1.85E-01	4.06E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	6.05E-01	-1.33E-01	-2.45E-01
Myelofibrosis	2A20.2	Whole blood	4.39E-02	-1.89E-01	-8.00E-01
Myocardial infarction	BA41-BA50	Peripheral blood	1.64E-02	3.12E-01	6.25E-01
Myopathy	8C70.6	Muscle tissue	1.80E-02	3.33E-01	1.12E+00
Neonatal sepsis	KA60	Whole blood	4.68E-29	9.98E-01	2.37E+00
Neuroectodermal tumour	2A00.11	Brain stem tissue	5.16E-03	1.98E-01	4.88E-01
Non-alcoholic fatty liver disease	DB92	Liver tissue	8.96E-01	-1.16E-01	-2.37E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	1.15E-01	2.32E-01	8.30E-01
Olive pollen allergy	CA08.00	Peripheral blood	2.19E-01	5.92E-01	7.59E-01
Oral cancer	2B6E	Oral tissue	6.02E-01	-1.15E-01	-1.80E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	1.50E-01	6.01E-01	7.13E-01
Osteoporosis	FB83.1	Bone marrow	3.51E-02	2.26E-01	2.04E+00
Ovarian cancer	2C73	Ovarian tissue	1.00E+00	1.26E-01	1.51E-01
Pancreatic cancer	2C10	Pancreas	1.88E-04	4.96E-01	1.08E+00
Parkinson's disease	8A00.0	Substantia nigra tissue	8.01E-01	-3.94E-02	-1.38E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	2.52E-04	3.33E-01	1.35E+00
Pituitary cancer	2D12	Pituitary tissue	5.23E-06	-1.28E+00	-2.58E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	1.98E-06	-1.67E+00	-4.31E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	5.91E-01	-1.43E-02	-4.47E-02
Polycythemia vera	2A20.4	Whole blood	8.65E-02	-8.08E-03	-3.57E-02
Pompe disease	5C51.3	Biceps muscle	2.34E-01	1.51E-01	5.12E-01
Preterm birth	KA21.4Z	Myometrium	9.07E-01	-1.70E-01	-4.10E-01
Prostate cancer	2C82	Prostate	5.28E-06	-9.96E-01	-1.46E+00
Psoriasis	EA90	Skin	8.69E-02	-1.76E-01	-3.46E-01
Rectal cancer	2B92	Rectal colon tissue	4.82E-01	-6.76E-02	-4.33E-01
Renal cancer	2C90-2C91	Kidney	1.62E-02	-4.13E-01	-9.05E-01
Retinoblastoma	2D02.2	Uvea	1.37E-04	9.69E-01	6.77E+00
Rheumatoid arthritis	FA20	Synovial tissue	2.88E-05	1.36E+00	3.72E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	1.83E-02	-7.90E-02	-3.93E-01
Schizophrenia	6A20	Prefrontal cortex	1.98E-01	1.27E-01	2.62E-01
Schizophrenia	6A20	Superior temporal cortex	9.48E-01	-3.94E-03	-3.86E-02
Scleroderma	4A42.Z	Whole blood	2.18E-02	-3.37E-01	-1.39E+00
Seizure	8A60-8A6Z	Whole blood	9.92E-01	-1.79E-02	-4.15E-02
Sensitive skin	EK0Z	Skin	6.82E-01	-6.60E-03	-1.99E-02
Sepsis with septic shock	1G41	Whole blood	5.73E-118	1.29E+00	3.59E+00
Shwachman-Diamond syndrome	3A70.0	Bone marrow	5.56E-01	-5.27E-01	-1.01E+00
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	6.95E-01	-1.58E-02	-8.67E-02
Simpson golabi behmel syndrome	LD2C	Adipose tissue	4.64E-01	-2.07E-02	-2.02E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	7.20E-01	-1.48E-01	-1.22E+00
Skin cancer	2C30-2C3Z	Skin	3.83E-07	-4.12E-01	-6.51E-01
Thrombocythemia	3B63	Whole blood	1.24E-02	-1.07E-01	-4.76E-01
Thrombocytopenia	3B64	Whole blood	3.56E-01	6.77E-01	5.88E-01
Thyroid cancer	2D10	Thyroid	4.42E-27	-1.12E+00	-1.44E+00
Tibial muscular dystrophy	8C75	Muscle tissue	2.29E-03	2.74E-01	7.46E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	5.90E-01	5.81E-02	2.21E-01
Type 2 diabetes	5A11	Liver tissue	3.07E-01	-6.27E-01	-8.99E-01
Ureter cancer	2C92	Urothelium	8.49E-01	-8.57E-03	-2.65E-02
Uterine cancer	2C78	Endometrium tissue	1.71E-09	-3.34E-01	-4.45E-01
Vitiligo	ED63.0	Skin	6.15E-01	2.45E-02	1.02E-01

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Cytochrome P450 reductase (P450) DTT Info
• DME DTT Type: Discontinued

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VTP-201227	DMFYM61	Psoriatic disorder	EA90	Discontinued in Phase 2	[1]
DuP-630	DM7YORJ	Dermatitis	EA80-EA89	Terminated	[2]
DuP-983	DM872CU	Pruritus	EC90	Terminated	[2]

References

• [1] VTP-201227. VietMedix.
• [2] CN patent application no. 1096855, Composition produced by treatment and induction of nitrogen mono oxide synthase expressed matter, and use thereof.
• [3] On the mechanism of the inactivation of the major phenobarbital-inducible isozyme of rat liver cytochrome P-450 by chloramphenicol. J Biol Chem. 1985 Jul 15;260(14):8397-403.
• [4] Lack of mechanism-based inactivation of rat hepatic microsomal cytochromes P450 by doxorubicin. Can J Physiol Pharmacol. 1999 Aug;77(8):589-97.
• [5] Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity. Arch Biochem Biophys. 1983 May;223(1):68-75.
• [6] Creatinine sulfate/esculoside/hesperidin methyl chalcone/menadiol sodium phosphate/tranexamic acid actions.
• [7] Generation of free radicals during the reductive metabolism of nilutamide by lung microsomes: possible role in the development of lung lesions in patients treated with this anti-androgen. Biochem Pharmacol. 1992 Feb 4;43(3):654-7.
• [8] Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity. Free Radic Biol Med. 2008 Mar 15;44(6):1169-79.
• [9] Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy. Pharmacogenet Genomics. 2017 Sep;27(9):337-346.
• [10] Characterization of the enzymes involved in the in vitro metabolism of amrubicin hydrochloride. Xenobiotica. 2005 Dec;35(12):1121-33.
• [11] Flavin-containing reductase: new perspective on the detoxification of nitrobenzodiazepine. Expert Opin Drug Metab Toxicol. 2010 Aug;6(8):967-81.