OSI-930

OSI-930 is a dual inhibitor of Kit (IC50s = 80 and 629 nM for the activated and non-activated kinase, respectively, in cell-free assays) and VEGFR2 (IC50 = 9 nM). It is selective for these kinases over a panel of 17 additional kinases (IC50s = 1.3->10 µM) but also inhibits VEGFR1, CSF1R, C-RAF, and LCK (IC50s = 8, 15, 41, and 22 nM, respectively). OSI-930 inhibits Kit autophosphorylation in NCI-H526 and HMC-1 cells expressing wild-type Kit and Kit containing the constitutively active V560G mutation (KitV560G), respectively, and stem cell factor-induced Kit autophosphorylation in NCI-H526 cells expressing wild-type Kit (IC50s = 58.1 and 78.9 nM, respectively). It also inhibits VEGF-induced autophosphorylation of VEGFR2 in human umbilical vein endothelial cells (HUVECs, IC50 = 64.4 nM). OSI-930 (100 nM) decreases endothelial sprout formation by greater than 50% in isolated rat aortic rings. It reduces tumor growth in a variety of mouse xenograft models, including colon and small-cell lung cancer, melanoma, and glioblastoma models, when administered orally at a dose of 200 mg/kg per day.Formal Name: 3-[(4-quinolinylmethyl)amino]-N-[4-(trifluoromethoxy)phenyl]-2-thiophenecarboxamide. CAS Number: 728033-96-3. Molecular Formula: C22H16F3N3O2S. Formula Weight: 443.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.33 mg/ml. lambdamax: 225, 276, 337 nm. SMILES: O=C(C1=C(C=CS1)NCC2=CC=NC3=C2C=CC=C3)NC4=CC=C(OC(F)(F)F)C=C4. InChi Code: InChI=1S/C22H16F3N3O2S/c23-22(24,25)30-16-7-5-15(6-8-16)28-21(29)20-19(10-12-31-20)27-13-14-9-11-26-18-4-2-1-3-17(14)18/h1-12,27H,13H2,(H,28,29). InChi Key: FGTCROZDHDSNIO-UHFFFAOYSA-N.