CB1954(Tretazicar (NSC-115829)), an anticancer prodrug, is activated by NAD(P)H quinone oxidoreductase 2. It is converted in the presence of the enzyme NQO2 and co-substrate caricotamide ( EP-0152R) (EP) into a potent cytotoxic bifunctional alkylating agent.

In the NPC cell line CNE1, toxic Tretazicar enhances cells killing. The overexpression of nitroreductase oxidored nitro domain-containing protein 1 (NOR1) reduce the 4 nitro group of Tretazicar, a potent cytotoxin, in order to convert the monofunctional alkylating agent Tretazicar into a toxic form. In the HepG2 cell line, the NOR1 gene upregulates of Grb2 expression and activates of MAPK signal transduction leading to enhances Tretazicar mediated cell cytotoxicity.

The NTR/CB1954 system, which is in a dose-dependent effect, are used for specific ablation of cells in vivo. NTR-mediated cell killing by CB1954, which is activated cross-links, presumed through triggers the apoptosis cascade resulting in rapid cell death. Selective and potent cells killing by NTR-CB1954 does not require a functional p53.

HepG2 cells,which are maintained in RPMI 1640 supplemented with 10% fetal calf serum (FCS) in a humidified culture incubator at 37?C with 5% CO2 and 95% air, grow to ~80% confluence are washed with PBS and treated with r CB1954(4-10 μmol/L) for 48hours.

RED 40 female mice,which express high levels of BLG-NTR transgene in the mammary gland and nontransgenic control mice on lactation day 6, were injected intraperitoneally （i.p.）with 50 mg/kg CB1954 dissolved in arachis oil containing 10% acetone.