Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM254EW)

• Drug Name: Nitrobenzodiazepine Drug Info
• Synonyms: nitrobenzodiazepine; NBDZ
• Cross-matching ID:
  PubChem CID: 25022001
  TTD Drug ID: DM254EW
  INTEDE Drug ID: DR2179

Molecule-Related Drug Atlas

Drug(s) Metabolized By NADPH-cytochrome P450 reductase (CPR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[3]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[4]
Nitrofurantoin	DM7PQIK	Urinary tract infection	GC08	Approved	[5]
Tacrolimus	DMZ7XNQ	Graft-versus-host disease	4B24	Approved	[6]
Benzphetamine	DMIJATC	Obesity	5B81	Approved	[7]
Nilutamide	DMFN07X	Prostate cancer	2C82.0	Approved	[8]
Menadiol sodium diphosphate	DMP9N85	Coagulation defect	3B10.0	Approved	[9]
Amrubicin	DM6SGUB	Small-cell lung cancer	2C25.Y	Phase 3	[10]

Drug(s) Metabolized By Oxygen-insensitive NADPH nitroreductase B (nfsB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitrofurazone	DMSM2KE	Skin burns	ME65.0	Approved	[11]
Nitrazepam	DMEGIQ6	Epilepsy	8A60-8A68	Approved	[11]
Flunitrazepam	DMGR5Z3	Insomnia	7A00-7A0Z	Approved	[2]
Clonazepam	DMTO13J	Absence epilepsy		Approved	[12]
CB1954	DMVP4YK	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[11]
Misonidazole	DMYB0HK	N. A.	N. A.	Investigative	[13]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
NADPH-cytochrome P450 reductase (CPR)	DE3N2FM	NCPR_HUMAN	Substrate	[1]
Oxygen-insensitive NADPH nitroreductase B (nfsB)	DE0QLUZ	NFSB_ECOLI	Substrate	[2]

References

• [1] Flavin-containing reductase: new perspective on the detoxification of nitrobenzodiazepine. Expert Opin Drug Metab Toxicol. 2010 Aug;6(8):967-81.
• [2] Structure-based development of bacterial nitroreductase against nitrobenzodiazepine-induced hypnosis. Biochem Pharmacol. 2012 Jun 15;83(12):1690-9.
• [3] Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity. Arch Biochem Biophys. 1983 May;223(1):68-75.
• [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] Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity. Free Radic Biol Med. 2008 Mar 15;44(6):1169-79.
• [6] Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy. Pharmacogenet Genomics. 2017 Sep;27(9):337-346.
• [7] 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.
• [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] Creatinine sulfate/esculoside/hesperidin methyl chalcone/menadiol sodium phosphate/tranexamic acid actions.
• [10] Characterization of the enzymes involved in the in vitro metabolism of amrubicin hydrochloride. Xenobiotica. 2005 Dec;35(12):1121-33.
• [11] Conversion of NfsB, a minor Escherichia coli nitroreductase, to a flavin reductase similar in biochemical properties to FRase I, the major flavin reductase in Vibrio fischeri, by a single amino acid substitution. J Bacteriol. 1996 Aug;178(15):4731-3.
• [12] Characterization of Escherichia coli nitroreductase NfsB in the metabolism of nitrobenzodiazepines. Biochem Pharmacol. 2009 Jul 1;78(1):96-103.
• [13] Metronidazole (flagyl) and misonidazole (Ro-07-0582): reduction by facultative anaerobes and cytotoxic action on hypoxic bacteria and mammalian cells in vivo. Br J Cancer Suppl. 1978 Jun;3:132-5.