Structural Basis for the Potent and Selective Inhibition of Casein Kinase 1 Epsilon

Casein kinase 1 epsilon (CK1 epsilon) and its closest homologue CK1 delta are key regulators of diverse cellular processes. We report two crystal structures of PF4800567, a potent and selective inhibitor of CK1 epsilon, bound to the kinase domains of human CK1 epsilon and CK1 delta as well as one apo CK1 epsilon crystal structure. These structures provide a molecular basis for the strong and specific inhibitor interactions with CK1 epsilon and suggest clues for further development of CK1 delta inhibitors.