Details of the Drug

General Information of Drug (ID: DMVP4YK)

Drug Name
CB1954
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]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 252.18
Logarithm of the Partition Coefficient (xlogp) 0
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C9H8N4O5
IUPAC Name
5-(aziridin-1-yl)-2,4-dinitrobenzamide
Canonical SMILES
C1CN1C2=C(C=C(C(=C2)C(=O)N)[N+](=O)[O-])[N+](=O)[O-]
InChI
InChI=1S/C9H8N4O5/c10-9(14)5-3-7(11-1-2-11)8(13(17)18)4-6(5)12(15)16/h3-4H,1-2H2,(H2,10,14)
InChIKey
WOCXQMCIOTUMJV-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
89105
CAS Number
21919-05-1
DrugBank ID
DB04253
TTD ID
D07ZHV
INTEDE ID
DR1787

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]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Biotransformations [7]
Ribosyldihydronicotinamide dehydrogenase (NQO2) OTGDAJRZ NQO2_HUMAN Biotransformations [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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 Demonstration of the activation of prodrug CB 1954 using human DT-diaphorase mutant Q104Y-transfected MDA-MB-231 cells and mouse xenograft model. Arch Biochem Biophys. 2001 Jan 1;385(1):203-8. doi: 10.1006/abbi.2000.2144.
8 Reduction and scavenging of chemically reactive drug metabolites by NAD(P)H:quinone oxidoreductase 1 and NRH:quinone oxidoreductase 2 and variability in hepatic concentrations. Chem Res Toxicol. 2018 Feb 19;31(2):116-126.