Small-Molecule Inhibitors of the Mcl-1 Oncoprotein

Mcl-1, an anti-apoptotic member of the Bcl-2 protein family, has emerged as an especially attractive target for the development of next generation antineoplastics owing to its direct involvement in tumor genesis as well as its role in the resistance of many cancers to current anti-cancer therapies. The efficacy of Navitoclax against a range of different cancer models that are dependent on Bcl-xL and Bcl-2, two relatives of Mcl-1, indicates that the inhibition of Mcl-1 with small-molecules might also be a viable strategy to kill cancer cells by inducing apoptosis. Herein, we provide a comprehensive review of the most potent, Mcl-1 selective small-molecule inhibitors reported in the literature to date.