Lucitanib

A dual inhibitor of VEGFR and FGFR, inhibits VEGFR1, VEGFR2, and VEGFR3 (IC50s = 7, 25, and 10 nM, respectively) and FGFR1 and FGFR2 (IC50s = 17.5 and 82.5 nM, respectively), selective for VEGFR1-3 and FGFR1-2 over FGFR3 and FGFR4 (IC50s = 237.5 and >1,000 nM, respectively), as well c-Kit, PDGFRalpha, and PDGFRbeta (IC50s = 456, 175, and 525 nM, respectively), but does inhibit FMS (IC50 = 5 nM), inhibits VEGF- or bFGF-induced HUVEC proliferation (IC50s = 40 and 50 nM, respectively) but inhibits the proliferation of A2780, A498, and SN12KI cancer cells only at higher concentrations (IC50s = 27.7, 19.6, and 12.79 µM, respectively), reduces tumor growth in various mouse xenograft models in a dose-dependent manner, completely inhibits bFGF-induced angiogenesis in a Matrigel(TM) plug assay in mice at 20 mg/kg. Formulation: A solid. InChI: InChI=1S/C26H25N3O4/c1-28-25(30)19-5-3-4-16-12-17(6-7-18(16)19)33-22-8-11-29-21-14-24(23(31-2)13-20(21)22)32-15-26(27)9-10-26/h3-8,11-14H,9-10,15,27H2,1-2H3,(H,28,30). InChIKey: CUDVHEFYRIWYQD-UHFFFAOYSA-N. SMILES: O=C(C1=CC=CC2=CC(OC3=CC=NC4=C3C=C(OC)C(OCC5(N)CC5)=C4)=CC=C21)NC