Selective Bisubstrate Inhibitors with Sub‐nanomolar Affinity for Protein Kinase Pim‐1

Potent and selective: The unique nature of the ATP binding pocket structure of Pim family protein kinases (PKs) was used for the development of bisubstrate inhibitors and a fluorescent probe with sub‐nanomolar affinity. Conjugates of arginine‐rich peptides with two ATP mimetic scaffolds were synthesized and tested as inhibitors of Pim‐1. Against a panel of 124 protein kinases, a novel ARC–PIM conjugate selectively inhibited PKs of the Pim family.