Discovery of a potent and selective c-Kit inhibitor for the treatment of inflammatory diseases

A potent and selective c-Kit inhibitor 20 was identified through a structure–activity relationship study. In an in vivo mouse model of mast cell activation, 20 blocked the SCF-induced histamine release with an EC50 of 26 nM.

Graphical abstractForm the screening of our kinase-preferred library, we have identified 1 as a potent small-molecule c-Kit inhibitor. Extensive structure–activity relationship study, incorporated with modification on PKDM properties have led to a selective c-Kit inhibitor 20. In an in vivo murine model of mast cell activation, 20 blocked the SCF-induced histamine release with an EC50 of 26 nM.Figure optionsDownload full-size imageDownload as PowerPoint slide