09 June 2010
Vol 2, Issue 35

About The Cover

Cover image expansion

ONLINE COVER Garnishing the Gatekeeper. The protein kinase inhibitor PLX4720 is shown bound to a mutated form of the BRAF kinase [BRAF(V600E)] in the vicinity of the gatekeeper residue. BRAF(V600E) is associated with approximately half of cutaneous melanomas, and gatekeeper mutations have been shown to specify resistance to kinase inhibitors. In this issue of Science Translational Medicine, Whittaker et al. present an elegant biochemical study that both reconciles the confusing history of RAF inhibitor development and provides an instructive framework for dissecting interactions between kinase drugs and their therapeutic targets. See also the accompanying Perspective by Garraway and Hahn. [CREDIT: COURTESY OF S. WHITTAKER AND R. MARAIS]