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Biochemical and biophysical characterization of unique switch pocket inhibitors of p38alpha
Herein we describe the identification and characterization of a class of molecules that are believed to extend into a region of p38 known as the ‘switch pocket’. Although these molecules lack a canonical hinge binding motif, they show Ki values as low as 100 nM against p38. We show that molecules that interact with this region of the protein demonstrate different binding kinetics than a canonical ATP mimetic, as well as a wide range of kinome profiles. Thus, the switch pocket presents new opportunities for kinome selectivity which could result in unique biochemical responses and offer new opportunities in the field of kinase drug discovery.
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Piperidine – Wikipedia,
Piperidine | C5H10413N – PubChem