Tivozanib (hydrate)

Tivozanib hydrate (AV-951 hydrate; KRN951 hydrate) is the hydrate form of Tivozanib (HY-10977). Tivozanib hydrate is a selective, orally active inhibitor for vascular endothelial growth factor receptor (VEGFR)-1, 2 3, with IC₅₀s of 30, 6.5 and 15 nM, respectively. Tivozanib hydrate exhibits antitumor efficacy^[1]. IC50 & Target:IC50: 30 nM (VEGFR 1), 6.5 (VEGFR 2), 15 nM (VEGFR 3)^[1] In Vitro:Tivozanib hydrate inhibits the phosphorylation of VEGFR-1, VEGFR-2, and VEGFR-3, with IC₅₀s of 0.16-0.24 nM^[1].
Tivozanib hydrate (0-100 nM, 24 h) inhibits VEGF-induced proliferation of HUVECs with IC₅₀ of 0.67 nM, and migration of HUVECs in dose-dependent manner^[1].
Tivozanib hydrate (0-300 nM, 1 h) selectively inhibits the VEGF-stimulated phosphorylation of MAPKs in endothelial cells ligand-dependently, with IC₅₀s of 0.13 and 0.18 nM for ERK1 and ERK2, respectively^[1]. In Vivo:Tivozanib hydrate (0.04-1 mg/kg, po for 14 days) exhibits antitumor efficacy against breast, colon,hepatic, lung, ovarian, pancreatic, and prostate cancer in model^[1].
Tivozanib hydrate (0.2-1 mg/kg, po for 21 days) reversibly suppresses vascular permeability and angiogenesis in Calu-6 tumor bearing rats model^[1].
Tivozanib hydrate (5 mg/kg, po, single dose) reveals a AUC_inf of 44.5 μg·h/mL, C_max of 2823 ng/mL in athymic mice model^[1].