Orantinib

252916-29-3

C18H18N2O3

DMSO : >= 28 mg/mL (90.22 mM)

Protein Tyrosine Kinase/RTK; Protein Tyrosine Kinase/RTK; Protein Tyrosine Kinase/RTK

Orantinib (SU6668; TSU-68) is a multi-targeted receptor tyrosine kinase inhibitor with K_is of 2.1 uM, 8 nM and 1.2 uM for Flt-1, PDGFRbeta and FGFR1, respectively. IC50 & Target: Ki: 0.008 uM (PDGFRbeta), 2.1 uM (Flt-1), 0.008 uM (FGFR1)^[1] In Vitro: Orantinib (SU6668; 0.03-10 uM) shows inhibitory activity against tyrosine phosphorylation of KDR in VEGF stimulated HUVECs, and also blocks PDGF-stimulated PDGFRbeta tyrosine phosphorylation in NIH-3T3 cells overexpressing PDGFRbeta. Orantinib (>=10 uM) inhibits acidic FGF-induced phosphorylation of the FGFR1 substrate 2. However, Orantinib (up to 100 uM) has no effect on EGF-stimulated EGFR tyrosine phosphorylation in NIH-3T3 cells overexpressing EGFR. Furthermore, Orantinib inhibits VEGF-driven and FGF-driven mitogenesis of HUVECs with mean IC₅₀ of 0.34 uM and 9.6 uM, respectively^[1]. In human myeloid leukemia MO7E cells, Orantinib (SU6668) inhibits the tyrosine autophosphorylation of stem cell factor (SCF) receptor, c-kit, with IC₅₀ of 0.1-1 uM, as well as ERK1/2 phosphorylation. In addition, Orantinib suppresses SCF-induced proliferation of MO7E cells with an IC₅₀ of 0.29 uM, and induces apoptosis^[2]. In Vivo: Orantinib (SU6668; 75-200 mg/kg) causes tumor growth inhibition on several tumor types in xenograft models in athymic mice, such as A375, Colo205, H460, Calu-6, C6, SF763T, and SKOV3TP5 cells. Orantinib (75 mg/kg) also inhibits tumor angiogenesis of C6 glioma xenografts^[1]. In a tumor model of HT29 human colon carcinoma, Orantinib (200 mg/kg) decreases the average vessel permeability and average fractional plasma volume in the tumor rim and core. Orantinib enhances abnormal stromal development at the periphery of carcinomas^[3]. Moreover, Orantinib (TSU-68; 200 mg/kg) augments the effect of chemotherapeutic infusion in a rabbit VX2 liver tumor model^[4].