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
UNII
7865D5D01M
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.