Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTOQ9GZ)

• DTT Name: Cytochrome P450 reductase (P450)
• Synonyms: P450R; NADPH--cytochrome P450 reductase; CYPOR; CPR
• Gene Name: POR
• DTT Type: Discontinued target; [1]
• BioChemical Class: NADH/NADPH oxidoreductase
• UniProt ID: NCPR_HUMAN
• TTD ID: T95446
• EC Number: EC 1.6.2.4
• 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. It can also provide electron transfer to heme oxygenase and cytochrome B5.
• Reactome Pathway: Cytochrome P450 - arranged by substrate type (R-HSA-211897)
• BioCyc Pathway: MetaCyc:HS05140-MON

Molecular Interaction Atlas (MIA) of This DTT

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	[2]
DuP-630	DM7YORJ	Dermatitis	EA80-EA89	Terminated	[3]
DuP-983	DM872CU	Pruritus	EC90	Terminated	[3]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Atopic dermatitis	EA90	Skin	4.68E-02	0.11	0.17
Breast cancer	2C82	Breast tissue	6.22E-08	0.29	0.46
Sensitive skin	EA90	Skin	6.82E-01	-0.01	-0.02

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: NADPH-cytochrome P450 reductase (CPR) DME Info
• Gene Name: POR

7 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Benzphetamine	DMIJATC	Obesity	5B81	Approved	[4]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[5]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[6]
Menadiol sodium diphosphate	DMP9N85	Coagulation defect	3B10.0	Approved	[7]
Nilutamide	DMFN07X	Prostate cancer	2C82.0	Approved	[8]
Nitrofurantoin	DM7PQIK	Urinary tract infection	GC08	Approved	[9]
Tacrolimus	DMZ7XNQ	Graft-versus-host disease	4B24	Approved	[10]

1 Clinical Trial Drug(s) Metabolized by This DTT

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

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitrobenzodiazepine	DM254EW	N. A.	N. A.	Investigative	[12]

References

• [1] Peritoneal cancer treatment with CYP2B1 transfected, microencapsulated cells and ifosfamide. Cancer Gene Ther. 2006 Jan 1;13(1):65-73.
• [2] VTP-201227. VietMedix.
• [3] CN patent application no. 1096855, Composition produced by treatment and induction of nitrogen mono oxide synthase expressed matter, and use thereof.
• [4] 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.
• [5] Lack of mechanism-based inactivation of rat hepatic microsomal cytochromes P450 by doxorubicin. Can J Physiol Pharmacol. 1999 Aug;77(8):589-97.
• [6] Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity. Arch Biochem Biophys. 1983 May;223(1):68-75.
• [7] Creatinine sulfate/esculoside/hesperidin methyl chalcone/menadiol sodium phosphate/tranexamic acid actions.
• [8] 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.
• [9] Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity. Free Radic Biol Med. 2008 Mar 15;44(6):1169-79.
• [10] Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy. Pharmacogenet Genomics. 2017 Sep;27(9):337-346.
• [11] Characterization of the enzymes involved in the in vitro metabolism of amrubicin hydrochloride. Xenobiotica. 2005 Dec;35(12):1121-33.
• [12] Flavin-containing reductase: new perspective on the detoxification of nitrobenzodiazepine. Expert Opin Drug Metab Toxicol. 2010 Aug;6(8):967-81.