Structure-based virtual screening approach to the discovery of p38 MAP kinase inhibitors

p38 Mitogen-activated protein kinase (MAPK) has been considered to be a promising target for the development of therapeutics for various immunologic diseases. Herein we report an example for a successful application of the virtual screening with protein–ligand docking to identify the novel inhibitors of p38α MAPK. These inhibitors were screened for having desirable physicochemical properties as a drug candidate and compound 1–3 revealed a moderate inhibitory activity with IC50 values ranging from 0.7 to 20 μM. Therefore, they deserve a consideration for further development by structure–activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are addressed in detail.

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