Sulfatinib (KDR-IN-1) (HMPL-012) is a potent and highly selective tyrosine kinase inhibitor against VEGFR1/2/3, FGFR1 and CSF1R with IC 50 s ranging from 1 to 24 nM.

Sulfatinib inhibits VEGFR1, 2, and 3, FGFR1 and CSF1R kinases with IC 50 s in a range of 1 to 24 nM. Sulfatinib strongly blocks VEGF induced VEGFR2 phosphorylation in HEK293KDR cells and CSF1 stimulated CSF1R phosphorylation in RAW264.7 cells with IC 50 of 2 and 79 nM, respectively. Sulfatinib also attenuates VEGF or FGF stimulated HUVEC cells proliferation with IC 50 < 50 nM [1]. Also, it is a hERG inhibitor with IC 50 of 6.8 μM in CHO cell [2].

In animal studies, a single oral dose of Sulfatinib effectively inhibits VEGFR2 phosphorylation stimulated by VEGF in lung tissues of nude mice in an exposure-dependent manner. Additionally, a rise in FGF23 plasma levels 24 hours after dosing indicates a suppression of FGFR signaling. Sulfatinib exhibits strong antitumor efficacy across various human xenograft models and significantly reduces CD31 expression, which evidences its potent antiangiogenic effects via the inhibition of VEGFR and FGFR signaling pathways. In the CT-26 syngeneic murine colon cancer model, Sulfatinib achieves moderate tumor growth inhibition following monotherapy. Moreover, after a 10 mg/kg oral dose, the AUC and C_max in mice are 397 ng/mL and 138 ng/mL, respectively [1].