SAR131675

SAR131675 is an ATP-competitive inhibitor of VEGF receptor 3 (VEGFR3) with an IC50 value of 23 nM for the human recombinant receptor in a cell-free assay. It is selective for VEGFR3 over VEGFR2 and VEGFR1 (IC50s = 230 and >3,000 nM, respectively). SAR131675 inhibits survival of human lymphatic cells cultured with the VEGFR3-specific ligands VEGF-C and VEGF-D over the non-specific ligand VEGF-A in vitro (IC50s = 14, 17, and 664 nM, respectively). It decreases VEGF-C and VEGF-A-induced migration of human microvascular endothelial cells (HMVECs) when used at concentrations of 100 and 300 nM. SAR131675 (100 mg/kg) reduces tumor size, decreases the number of pancreatic angiogenic islets, and increases survival in the RIP1-Tag2 transgenic mouse model of pancreatic neuroendocrine tumors. It also decreases tumor size, levels of VEGFR3 in mammary tumor lysates, number of tumor-associated macrophages in mammary tumors, and the number of lung metastases in a 4T1 mouse allograft model when administered at a dose of 100 mg/kg.Formal Name: 2-amino-1-ethyl-1,4-dihydro-7-[(3R)-3-hydroxy-4-methoxy-3-methyl-1-butyn-1-yl]-N-methyl-4-oxo-1,8-naphthyridine-3-carboxamide. CAS Number: 1433953-83-3. Molecular Formula: C18H22N4O4. Formula Weight: 358.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: Chloroform: 30 mg/ml. lambdamax: 230, 257, 328, 340 nm. SMILES: COC[C@@](O)(C)C#CC1=NC(N(CC)C(N)=C(C(NC)=O)C2=O)=C2C=C1. InChi Code: InChI=1S/C18H22N4O4/c1-5-22-15(19)13(17(24)20-3)14(23)12-7-6-11(21-16(12)22)8-9-18(2,25)10-26-4/h6-7,25H,5,10,19H2,1-4H3,(H,20,24)/t18-/m1/s1. InChi Key: PFMPOBVAYMTUOX-GOSISDBHSA-N.