ODM-203

ODM-203 is a dual inhibitor of VEGFR and FGFR (IC50s = 5-26 and 6-35 nM for VEGFR1-3 and FGFR1-4, respectively). It is selective for VEGFR1-3 and FGFR1-4 over a panel of 308 kinases at 1 µM, but does inhibit the receptor tyrosine kinases PDGFRalpha, PDGFRbeta, and DDR1 (IC50s = 35, 169, and 6 nM, respectively), as well as MAP4K4, MINK1, RET, SIK2, YES1, and Tie2 (IC50s = 49, 41, 8, 23, 152, and 174 nM, respectively). ODM-203 inhibits FGFR-dependent proliferation in H1581 lung, SNU-16 stomach, and RT4 bladder cancer cells (IC50s = 104, 132, and 192 nM, respectively) and VEGF-induced tube formation by human umbilical vein endothelial cells (HUVECs, IC50 = 33 nM). In vivo, ODM-203 (20 and 40 mg/kg) decreases tumor volume in an RT4 mouse xenograft model. It also reduces tumor growth and intratumor phosphorylation of FGFR in a SNU-16 mouse xenograft model when administered at a dose of 30 mg/kg.Formal Name: N-[2',4'-difluoro-5-[5-(1-methyl-1H-pyrazol-4-yl)-1H-benzimidazol-1-yl][1,1'-biphenyl]-3-yl]-cyclopropanesulfonamide. CAS Number: 1430723-35-5. Molecular Formula: C26H21F2N5O2S. Formula Weight: 505.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 2 mg/ml, DMSO: 10 mg/ml, DMSO:PBS (pH 7.2) (1:3): 0.25 mg/ml. lambdamax: 239 nm. SMILES: FC(C=C1)=CC(F)=C1C2=CC(NS(C3CC3)(=O)=O)=CC(N4C=NC5=CC(C6=CN(C)N=C6)=CC=C54)=C2. InChi Code: InChI=1S/C26H21F2N5O2S/c1-32-14-18(13-30-32)16-2-7-26-25(10-16)29-15-33(26)21-9-17(23-6-3-19(27)11-24(23)28)8-20(12-21)31-36(34,35)22-4-5-22/h2-3,6-15,22,31H,4-5H2,1H3. InChi Key: ZJFCBQXPTQSTCZ-UHFFFAOYSA-N.