Many small mols. possess anti-cancer activity but frequently display high levels of toxicity.Kevetrin, a small mol. with broad spectrum anti-cancer activity in xenograft tumor models (lung, breast, colon, prostate, squamous cell, and leukemia), was well tolerated with low toxicity.Cytotoxicity assays revealed a relatively low potency in vitro and yet Kevetrin was efficacious against multi-drug resistant tumors.Kevetrin inhibits tumor growth by arresting cells in the G2/M stage of cell division together with increased apoptosis.Cell cycle arrest was associated with a change in levels of G2/M proteins (CDK1, cdc25B and WEE1) and cell death was promoted by pro-apoptotic signaling (p53, MDM2, p21 and PUMA) that together affect the metabolic pathways in cancer cells.This presentation will discuss the SAR, mechanism of action, anti-tumor activity, pre-clin. pharmacol., and safety profiles that led to the advancement of Kevetrin into Phase I clin. trials.