SAR131675

SAR131675 is the first highly specific VEGFR-3-TK inhibitor, which displaying significant antitumoral and antimetastatic activities in vivo through inhibition of lymphangiogenesis and TAM invasion. SAR131675 inhibited VEGFR-3 tyrosine kinase activity and VEGFR-3 autophosphorylation in HEK cells with IC50 values of 20 and 45 nmol/L, respectively. SAR131675 dose dependently inhibited the proliferation of primary human lymphatic cells, induced by the VEGFR-3 ligands VEGFC and VEGFD, with an IC50 of about 20 nmol/L. SAR131675 showed a potent antitumoral effect in several orthotopic and syngenic models, including mammary 4T1 carcinoma and RIP1.Tag2 tumors. Interestingly, SAR131675 significantly reduced lymph node invasion and lung metastasis, showing its antilymphangiogenic activity in vivo. SAR131675 significantly reduced TAM infiltration and aggregation in 4T1 tumors.