For research use only. Not for therapeutic Use.
Tretazicar (CB 1954), an antitumor proagent, is highly selective against the Walker 256 rat tumour line. Tretazicar is enzymatically activated to generate a bifunctional agent, which can form DNA-DNA interstrand cross-links. Tretazicar in rat cells involves the reduction of its 4-nitro group to a 4-hydroxylamine by the enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1)[1][2].
Tretazicar (CB 1954) (0.1-1000 μM; 3 days) has sensitivity for retrovirally transduced AB22 (AB22-nr) cells with an IC50 of 3 μM[3].
DNA cross-link formation in affected cells is a result of the bioactivation of the drug by the enzyme DT diaphorase (NAD(P)H dehydro-genase (quinone)) in the Walker cells which reduces the 4-nitro group of Tretazicar. The product of this reaction is a difunctional alkylating agent, 5-aziridin-1-yl-4-hydroxylamino-2-nitrobenzamide[4].
Tretazicar (CB 1954) (80 mg/kg; i.p. on days 2 and 9) results in a significant increase in survival[3].
| Catalog Number | R016430 |
| CAS Number | 21919-05-1 |
| Synonyms | 5-(aziridin-1-yl)-2,4-dinitrobenzamide |
| Molecular Formula | C9H8N4O5 |
| Purity | ≥95% |
| 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 |
| SMILES | C1CN1C2=C(C=C(C(=C2)C(=O)N)[N+](=O)[O-])[N+](=O)[O-] |
| Reference | [1]. Knox RJ,et al. Bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by human NAD(P)H quinone oxidoreductase 2: a novel co-substrate-mediated antitumor prodrug therapy. Cancer Res. 2000 Aug 1;60(15):4179-86. [2]. Knox RJ, et al. CB 1954: from the Walker tumor to NQO2 and VDEPT. Curr Pharm Des. 2003;9(26):2091-104. [3]. Green NK, et al. Immune enhancement of nitroreductase-induced cytotoxicity: studies using a bicistronicadenovirus vector. Int J Cancer. 2003 Mar 10;104(1):104-12. [4]. Drabek D, et al. The expression of bacterial nitroreductase in transgenic mice results in specific cell killing by the prodrug CB1954. Gene Ther. 1997 Feb;4(2):93-100. |
