Issues

The cover features three related studies investigating inhibitors of the antiapoptotic BCL2 family protein MCL1. Ramsey and colleagues used fragment-based methods and structure-based design to discover VU661013, a potent, selective small-molecule MCL1 inhibitor that synergized with BCL2 inhibition in models of acute myeloid leukemia. Caenepeel and colleagues identified an orally bioavailable selective MCL1 inhibitor, AMG 176, that triggered apoptosis in hematologic malignancies. Nangia, Siddiqui, and colleagues found that dual inhibition of MCL1 and MEK suppressed the growth of KRAS-mutant lung tumors. Collectively, these findings indicate that MCL1 inhibitors may be beneficial alone or in combination therapies to treat patients with a variety of malignancies. For details, please see the articles by Ramsey and colleagues on page 1566, Caenepeel and colleagues on page 1582, and Nangia, Siddiqui, and colleagues on page 1598.