“Drugging Protein Kinases: Conformational Control and Chemical Knockdown”

 My lab uses chemical synthesis to develop novel tools to interrogate the regulation and role of protein kinases in human disease. In this talk, I will highlight our ongoing work with developing conformation-selective inhibitors of protein kinases. I will discuss conformation-selective dasatinib analogs and how conformation impacts pharmacological and kinase-specific properties including kinome-wide selectivity. I will also discuss applications of double-drugging protein kinases where conformation dictates allosteric ligand occupancy. Finally, I will discuss the promise of kinase directed PROTACs as tools for the chemical knockdown of protein kinases.