Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR1787)
Drug Name
CBL-954
Synonyms
Tretazicar; Tretazicar [INN]; 2,4-Dinitro-5-ethyleneiminobenzamide; 2,4-Dinitroethyleneiminobenzamide; 21919-05-1; 5-(1-Aziridinyl)-2,4-dinitrobenzamide; 5-(AZIRIDIN-1-YL)-2,4-DINITROBENZAMIDE; 5-Aziridino-2,4-dinitrobenzamide; 5-Aziridinyl-2,4-dinitrobenzamide; 5-[aziridin-1-yl]-2,4-dinitrobenzamide; 7865D5D01M; BRN 5825582; Benzamide, 5-(1-aziridinyl)-2,4-dinitro-; Benzamide,5-(1-aziridinyl)-2,4-dinitro-; C9H8N4O5; CB 1954; CB-1954; CB1; CB1954; CCRIS 1631; CHEMBL23330; NSC 115829; SMR000326847; UNII-7865D5D01M
Indication Hepatocellular carcinoma [ICD11: 2C12] Discontinued [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 252.18 Topological Polar Surface Area 138
Heavy Atom Count 18 Rotatable Bond Count 2
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 6
Cross-matching ID
PubChem CID
89105
PubChem SID
411933 ; 822628 ; 5274718 ; 6436374 ; 7886475 ; 10223498 ; 11110923 ; 11404752 ; 14774371 ; 17404763 ; 24278301 ; 26714457 ; 44420234 ; 46500339 ; 46509068 ; 47193717 ; 47662830 ; 49875678 ; 50105941 ; 50105942 ; 53777306 ; 57309661 ; 57334580 ; 75479679 ; 85230965 ; 90341816 ; 92303533 ; 103141765 ; 103191314 ; 103918267 ; 104038062 ; 104398392 ; 117379122 ; 121360965 ; 124749537 ; 124800452 ; 124879594 ; 127316104 ; 127316105 ; 127316106 ; 127316107 ; 127316108 ; 127316109 ; 127316110 ; 129609567 ; 135045423 ; 137016521 ; 138030325 ; 160967301 ; 162816292
CAS Number
21919-05-1
TTD Drug ID
D07ZHV
Formula
C9H8N4O5
Canonical SMILES
C1CN1C2=C(C=C(C(=C2)C(=O)N)[N+](=O)[O-])[N+](=O)[O-]
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
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
2-NHOH DM005554
10105600
Unclear 1 [4]
4-NHOH DM005555
5487972
Unclear 1 [4]
The hydroxylamine metabolite DM005556 N. A. Unclear 1 [8]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR005921 CBL-954 2-NHOH Unclear NfsA [4]
MR005922 CBL-954 4-NHOH Unclear YfkO [4]
MR005923 CBL-954 The hydroxylamine metabolite Unclear nfsB [8]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Azoreductase (azoR) DME1096 Escherichia coli
AZOR_ECOLI
1.7.1.6
[2]
General stress protein 14 (ywrO) DME1302 Bacillus subtilis
GS14_BACSU
1.6.99.-
[3]
N-ethylmaleimide reductase (nemA) DME1097 Escherichia coli
NEMA_ECOLI
1.3.1.-
[2]
Oxygen-insensitive NADPH nitroreductase A (nfsA) DME1098 Escherichia coli
NFSA_ECOLI
1.5.1.38
[2]
Oxygen-insensitive NADPH nitroreductase A (nfsA) DME1098 Escherichia coli
NFSA_ECOLI
1.5.1.38
[4]
Oxygen-insensitive NADPH nitroreductase B (nfsB) DME1048 Escherichia coli
NFSB_ECOLI
1.5.1.34
[5] , [2]
Putative NAD(P)H nitroreductase YfkO (yfkO) DMEN308 Bacillus subtilis
YFKO_BACSU
1.-.-.-
[4]
Quinone reductase 1 (NQO1) DME0097 Homo sapiens
NQO1_HUMAN
1.6.5.2
[6]
Unclear metabolic mechanism (DME-unclear) DME1388 Bifidobacterium breve Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1435 Lactobacillus reuteri Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1438 Lactococcus lactis Not Available Not Available [7]
⏷ Show the Full List of 11  DME(s)
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 Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954. Biochem Pharmacol. 2010 Mar 1;79(5):678-87.
3 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.
4 uvrB gene deletion enhances SOS chromotest sensitivity for nitroreductases that preferentially generate the 4-hydroxylamine metabolite of the anti-cancer prodrug CB1954
5 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.
6 Gene Therapy of the Central Nervous System. Charter 22 - Prodrug-Activation Gene Therapy. 2006, Pages 291-301
7 Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria. J Control Release. 2016 Jan 28;222:9-17.
8 Bystander or no bystander for gene directed enzyme prodrug therapy

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