Selective degradation of CDK6 by a palbociclib based PROTAC.

Basic Information

ID: ALA4340529

Journal: Bioorg Med Chem Lett

Title: Selective degradation of CDK6 by a palbociclib based PROTAC.

Authors: Rana S, Bendjennat M, Kour S, King HM, Kizhake S, Zahid M, Natarajan A.

Abstract: Development of selective kinase inhibitors that target the ATP binding site continues to be a challenge largely due to similar binding pockets. Palbociclib is a cyclin-dependent kinase inhibitor that targets the ATP binding site of CDK4 and CDK6 with similar potency. The enzymatic function associated with the kinase can be effectively probed using kinase inhibitors however the kinase-independent functions cannot. Herein, we report a palbociclib based PROTAC that selectively degrades CDK6 while sparing the homolog CDK4. We used competition studies to characterize the binding and mechanism of CDK6 degradation.

CiteXplore: 30935795

DOI: 10.1016/j.bmcl.2019.03.035

Patent ID: ┄