Structural basis for the potent and selective inhibition of casein kinase 1 epsilon.

Casein kinase 1 epsilon (CK1e) and its closest homologue CK1δ are key regulators of diverse cellular processes. We report two crystal structures of PF4800567, a potent and selective inhibitor of CK1e, bound to the kinase domains of human CK1e and CK1δ as well as one apo CK1e crystal structure. These structures provide a molecular basis for the strong and specific inhibitor interactions with CK1e and suggest clues for further development of CK1δ inhibitors.