FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated schwannomas

Abstract

Background:The PAKs are effectors of Rac/cdc42. Results:Identification of a pyridopyrimidinone, as a potent inhibitor of the group I PAKs that shows anti-tumor activityin vivo. Conclusion:A pyridopyrimidinone provides a scaffold for development of high specificity group I PAK inhibitors. Significance: Identification class of orally available ATP-competitive Group I PAK inhibitors with significant potential for the treatment of NF2. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.