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

General Information of Drug (ID: DMVP4YK)

• Drug Name: CB1954 Drug Info
• Synonyms: Tretazicar; CB 1954; 21919-05-1; CB1954; 5-(1-Aziridinyl)-2,4-dinitrobenzamide; 5-Aziridino-2,4-dinitrobenzamide; CB-1954; 5-(AZIRIDIN-1-YL)-2,4-DINITROBENZAMIDE; 5-Aziridinyl-2,4-dinitrobenzamide; Tretazicar [INN]; 2,4-Dinitroethyleneiminobenzamide; 2,4-Dinitro-5-ethyleneiminobenzamide; CHEMBL23330; CCRIS 1631; UNII-7865D5D01M; NSC 115829; 7865D5D01M; BRN 5825582; Benzamide,5-(1-aziridinyl)-2,4-dinitro-; Benzamide, 5-(1-aziridinyl)-2,4-dinitro-; CB1; C9H8N4O5; SMR000326847; aziridine dinitrobenzamide; CB1954(Tretazicar); AC1Q1YAR

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 89105
  CAS Number: CAS 21919-05-1
  TTD Drug ID: DMVP4YK
  INTEDE Drug ID: DR1787

Molecule-Related Drug Atlas

Drug(s) Targeting Quinone reductase 2 (NQO2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Melatonin	DMKWFBT	Depression	6A70-6A7Z	Approved	[7]
NSC-645809	DMPJQZG	Breast cancer	2C60-2C65	Phase 2	[8]
Prolarix	DMZIQ8G	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
Flavin-Adenine Dinucleotide	DM5S4GK	Discovery agent	N.A.	Investigative	[2]
2-iodo-melatonin	DMSEIUP	Discovery agent	N.A.	Investigative	[10]
3,4,5-Trimethoxy-4'-amino-trans-stilbene	DMDBOJ5	Discovery agent	N.A.	Investigative	[11]
NSC-645808	DMMBAR3	Discovery agent	N.A.	Investigative	[8]
decynium 22	DMWCTZ7	Discovery agent	N.A.	Investigative	[12]
NSC-106080	DMR6P9S	Discovery agent	N.A.	Investigative	[12]
NSC-99528	DMXZAIG	Discovery agent	N.A.	Investigative	[12]

Drug(s) Metabolized By Quinone reductase 1 (NQO1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[13]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[14]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[14]
Carboplatin	DMG281S	Adenocarcinoma	2D40	Approved	[14]
Beta-Lapachone	DMMI84K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[15]
Nitrobenzanthrone	DMN6L70	N. A.	N. A.	Investigative	[16]

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	[4]
Nitrazepam	DMEGIQ6	Epilepsy	8A60-8A68	Approved	[4]
Flunitrazepam	DMGR5Z3	Insomnia	7A00-7A0Z	Approved	[17]
Clonazepam	DMTO13J	Absence epilepsy		Approved	[18]
Nitrobenzodiazepine	DM254EW	N. A.	N. A.	Investigative	[17]
Misonidazole	DMYB0HK	N. A.	N. A.	Investigative	[19]

Drug(s) Metabolized By Azoreductase (azoR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Balsalazide	DM7I1T9	Inflammatory bowel disease	DD72	Approved	[20]
CTK0H-9987	DMSGYNP	N. A.	N. A.	Phase 2	[21]
SC-47085	DMGH4Q0	N. A.	N. A.	Phase 2	[22]
Ipsalazide	DMYEM59	N. A.	N. A.	Investigative	[20]

Drug(s) Metabolized By Oxygen-insensitive NADPH nitroreductase A (nfsA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitrofurazone	DMSM2KE	Skin burns	ME65.0	Approved	[23]
Nitrazepam	DMEGIQ6	Epilepsy	8A60-8A68	Approved	[23]
Loperamide	DMOJZQ9	Diarrhea	ME05.1	Approved	[24]
HSDB-674	DMJG4WR	N. A.	N. A.	Phase 1	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Quinone reductase 2 (NQO2)	TTJLP0R	NQO2_HUMAN	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Quinone reductase 1 (NQO1)	DENP5RY	NQO1_HUMAN	Substrate	[3]
Oxygen-insensitive NADPH nitroreductase B (nfsB)	DE0QLUZ	NFSB_ECOLI	Substrate	[4] , [5]
Oxygen-insensitive NADPH nitroreductase A (nfsA)	DEDPI65	NFSA_ECOLI	Substrate	[5]
N-ethylmaleimide reductase (nemA)	DE1FR8H	NEMA_ECOLI	Substrate	[5]
Azoreductase (azoR)	DEEHWOG	AZOR_ECOLI	Substrate	[5]
General stress protein 14 (ywrO)	DE07EIQ	GS14_BACSU	Substrate	[6]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019051)
• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] Gene Therapy of the Central Nervous System. Charter 22 - Prodrug-Activation Gene Therapy. 2006, Pages 291-301
• [4] 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.
• [5] Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954. Biochem Pharmacol. 2010 Mar 1;79(5):678-87.
• [6] Bacillus amyloliquefaciens orthologue of Bacillus subtilis ywrO encodes a nitroreductase enzyme which activates the prodrug CB 1954. Microbiology. 2002 Jan;148(Pt 1):297-306.
• [7] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [8] Imidazoacridin-6-ones as novel inhibitors of the quinone oxidoreductase NQO2. Bioorg Med Chem Lett. 2010 May 1;20(9):2832-6.
• [9] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [10] Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities. J Med Chem. 2009 Apr 9;52(7):1873-84.
• [11] Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer. Bioorg Med Chem. 2010 Jul 15;18(14):5352-66.
• [12] In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
• [13] Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52.
• [14] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
• [15] Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice. PLoS One. 2012;7(10):e47122.
• [16] Dose-dependent response to 3-nitrobenzanthrone exposure in human urothelial cancer cells. Chem Res Toxicol. 2017 Oct 16;30(10):1855-1864.
• [17] Structure-based development of bacterial nitroreductase against nitrobenzodiazepine-induced hypnosis. Biochem Pharmacol. 2012 Jun 15;83(12):1690-9.
• [18] Characterization of Escherichia coli nitroreductase NfsB in the metabolism of nitrobenzodiazepines. Biochem Pharmacol. 2009 Jul 1;78(1):96-103.
• [19] 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.
• [20] Studies of two novel sulfasalazine analogs, ipsalazide and balsalazide. Dig Dis Sci. 1983 Jul;28(7):609-15.
• [21] The role of the gut flora in the metabolism of prontosil and neoprontosil in the rat. Xenobiotica. 1971 Mar;1(2):143-56.
• [22] Olsalazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in inflammatory bowel disease. Drugs. 1991 Apr;41(4):647-64.
• [23] Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase. J Bacteriol. 1996 Aug;178(15):4508-14.
• [24] Reduction of the prodrug loperamide oxide to its active drug loperamide in the gut of rats, dogs, and humans. Drug Metab Dispos. 1995 Mar;23(3):354-62.
• [25] Absorption of (-)-nicotine-l-N-oxide in man and its reduction in the gastrointestinal tract. J Pharm Pharmacol. 1970 Sep;22(9):722-3.