SG3199 is a PBD dimer which binds in the minor groove of DNA, and forms covalent DNAinterstrandcross-links in naked linear plasmid DNA. SG3199 is potently cytotoxic against a panel of human solid tumour and haematological cancer cell lines.
Porfiromycin is a n N-methyl derivative of the antineoplastic antibiotic mitomycin C isolated from the bacterium Streptomyces ardus and other Streptomyces bacterial species. Bioreduced porfiromycin generates oxygen radicals and alkylates DNA, producing interstrandcross-links and single-strand breaks, thereby inhibiting DNA synthesis. Porfiromycin is preferentially toxic to hypoxic cells.
Caricotamide is a synthetic co-substrate that activates the human endogenous enzyme NRH:quinone oxidoreductase 2 (NQO2) with potential chemoadjuvant activity. When caricotamide is administered simultaneously with the prodrug tretazicar, NQO2 converts tretazicar to the bifunctional alkylating agent dinitrobenzamide, which is capable of forming a high degree of DNAinterstrandcross-links, resulting in the inhibition of DNA replication and the induction of apoptosis. NQO2 has been found to be over-expressed in cancers such as hepatocellular carcinoma (HCC), colorectal and ovarian cancers.