PI3Kδ-IN-1

Description: PI3Kdelta-IN-1 is a novel, potent, selective, and efficacious PI3Kdelta inhibitor with an IC50 of 1.7 nM. PI3Kdelta plays an important role controlling immune cell function and has therefore been identified as a potential target for the treatment of immunological disorders. PI3Kdelta-IN-1 improved Caco-2 permeability, reduced Caco-2 efflux, reduced hERG PC activity, and increased selectivity profile while maintaining potency in the CD69 hWB assay. The optimization of the aryl substitution then identified a 4'-CN group that improved the human/rodent correlation in microsomal metabolic stability. PI3Kdelta-IN-1 is very potent in PK/PD assays and highly efficacious in a mouse collagen-induced arthritis model.

References: J Med Chem. 2017 Jun 22; 60(12):5193-5208.