Lucitanib (hydrochloride)

Lucitanib is a dual inhibitor of VEGFR and FGFR that inhibits VEGFR1, VEGFR2, and VEGFR3 (IC50s = 7, 25, and 10 nM, respectively) and FGFR1 and FGFR2 (IC50s = 17.5 and 82.5 nM, respectively). It is selective for these receptors over FGFR3 and FGFR4 (IC50s = 237.5 and >1,000 nM, respectively), as well as the PDGFR family members c-Kit, PDGFRalpha, and PDGFRbeta (IC50s = 456, 175, and 525 nM, respectively), but does inhibit FMS, also known as CSF-1 receptor tyrosine kinase (IC50 = 5 nM). Lucitanib inhibits the proliferation of human umbilical vein endothelial cells (HUVECs) induced by VEGF or basic FGF (bFGF, IC50s = 40 and 50 nM, respectively) but inhibits the proliferation of A2780 ovarian, A498 renal, and SN12KI renal cancer cells only at higher concentrations (IC50s = 27.7, 19.6, and 12.79 µM, respectively). It reduces tumor growth in HT-29 colon and A2780 ovarian cancer mouse xenograft models, as well as in RXF 393, A498, and SKN12I renal cancer mouse xenograft models in a dose-dependent manner. It also completely inhibits bFGF-induced angiogenesis in a Matrigel(TM) plug assay in mice when administered at a dose of 20 mg/kg.Formal Name: 6-[[7-[(1-aminocyclopropyl)methoxy]-6-methoxy-4-quinolinyl]oxy]-N-methyl-1-naphthalenecarboxamide, dihydrochloride. CAS Number: 2108875-91-6. Synonyms: AL 3810, E-3810. Molecular Formula: C26H25N3O4 . 2HCl. Formula Weight: 516.4. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: Slightly Soluble, DMSO: 5 mg/ml, Ethanol: Slightly Soluble, PBS (pH 7.2): Slightly Soluble. SMILES: O=C(C1=CC=CC2=CC(OC3=CC=NC4=C3C=C(OC)C(OCC5(CC5)N)=C4)=CC=C21)NC.Cl.Cl. InChi Code: InChI=1S/C26H25N3O4.2ClH/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),2*1H. InChi Key: GJYKJPXOPZOBBC-UHFFFAOYSA-N.