2015 Volume 25 Issue 3 Pages 150-157
FGFRs belong to the family of receptor tyrosine kinase that regulates multiple biological processes, such as cell proliferation and migration. Various genetic alterations as well as overexpression of FGFRs in a subset of tumors have been reported, and these genetic alterations are suggested to be associated with tumor growth and survival. We have discovered an orally available and selective inhibitor of FGFR1, 2, and 3, named CH5183284/Debio 1347. The hit compound was identified from our original compound library by a high throughput screening program. Chemical modifications utilizing 3D-modeling analyses of the hit compound and its derivatives with FGFR1 were mainly aimed at enhancing activity that was selective to FGFRs. CH5183284/Debio 1347 showed antitumor activity against cancer cell lines with genetic alterations in FGFRs both in vitro and in vivo in xenograft mice models.
