laromustine + temozolomide

Laromustine + temozolomide is an investigational combination of two alkylating agents used in the treatment of hematologic malignancies and explored for other cancers. Laromustine (VNP40101M) is a novel alkylating agent that induces DNA cross-linking and cytotoxicity. Temozolomide is an imidazotetrazine prodrug that methylates DNA at the O6 and N7 positions of guanine residues after conversion to its active metabolite; this leads to DNA damage and apoptosis. Resistance to alkylators like laromustine can be mediated by O6-alkylguanine-DNA alkyltransferase (AGT), but temozolomide depletes AGT levels, thereby sensitizing tumor cells to laromustine’s effects. The combination has been studied in phase I trials for relapsed/refractory leukemia with evidence of antitumor activity[1]. Both drugs are small molecules administered systemically.

Brand names

Temomedac

Other names

laromustine + TMZ