Pharmacology of ME-344, a novel cytotoxic isoflavone
Isoflavones derived from plants in the Fabaceae (formerly Leguminosae) family have been recognized for their phytoestrogenic properties, and certain derivatives have also demonstrated potential as cancer therapeutic agents. ME-344, a second-generation isoflavone related to phenoxodiol (Fig. 1), has undergone both preclinical and early clinical testing. This drug exhibits unique cytotoxicity profiles, with cancer cell lines either being intrinsically sensitive or resistant to it. Research indicates that ME-344’s cytotoxic effects are primarily mediated through targeting mitochondrial bioenergetics. While the drug has completed early Phase I/II trials in solid tumors, with some evidence of disease response and minimal dose-limiting toxicities, there is still a pressing need to identify specific cellular targets that influence sensitivity. The long-term goal is to leverage this information for personalized therapy. This review summarizes existing and ongoing studies that are contributing to the continued development of ME-344, potentially leading to New Drug Application (NDA) approval.