Information
Orantinib (TSU-68, SU6668) has greatest potency againstPDGFRautophosphorylation withKiof 8 nM in a cell-free assay, but also strongly inhibits Flk-1 and FGFR1 trans-phosphorylation, little activity against IGF-1R, Met, Src, Lck, Zap70, Abl and CDK2; does
In vitro
TSU-68 is a competitive inhibitor, with regard to ATP, to Flk-1/KDR trans-phosphorylation, FGFR1 trans-phosphorylation, and PDGFRβ kinases autophosphorylation. TSU-68 (0.03-10 μM) inhibits tyrosine phosphorylation of KDR in VEGF stimulated HUVECs. TSU-68 also inhibits PDGF-stimulated PDGFRβ tyrosine phosphorylation in NIH-3T3 cells overexpressing PDGFRβ at a minimum concentration of 0.03-0.1 μM. TSU-68 inhibits acidic FGF-induced phosphorylation of the FGFR1 substrate 2 at 10 μM and higher. However, TSU-68 (up to 100 μM) has no effect on EGF-stimulated EGFR tyrosine phosphorylation in NIH-3T3 cells overexpressing EGFR. TSU-68 inhibits VEGF-driven and FGF-driven mitogenesis of HUVECs with mean IC50 of 0.34 μM and 9.6 μM, respectively. In human myeloid leukemia MO7E cells, TSU-68 inhibits the tyrosine autophosphorylation of stem cell factor (SCF) receptor, c-kit, with IC50 of 0.1-1 μM, as well as ERK1/2 phosphorylation, a signaling event downstream of c-kit activation. TSU-68 also inhibits SCF-induced proliferation of MO7E cells with IC50 of 0.29 μM, and induces apoptosis.
In vivo
TSU-68 (75-200 mg/kg) induces tumor growth inhibition against a broad range of tumor types in xenograft models in athymic mice, including A375, Colo205, H460, Calu-6, C6, SF763T, and SKOV3TP5 cells. TSU-68 (75 mg/kg) also suppresses tumor angiogenesis of C6 glioma xenografts. In a tumor model of HT29 human colon carcinoma, TSU-68 (200 mg/kg) decreases the average vessel permeability and average fractional plasma volume in the tumor rim and core. TSU-68 promotes abnormal stromal development at the periphery of carcinomas. In a rabbit VX2 liver tumor model, TSU-68 (200 mg/kg) augments the effect of chemotherapeutic infusion.
Cell Data
cell lines：MCF-7, LNCAP, PC3, HCT116, CACO-2, A549, HL60, K562 cells and et al.
Concentrations：0.03-10 μM , dissolved in DMSO as 10 mM stock solution
Incubation Time：1 hour (before ligand stimulation)
Powder Purity:≥99%
H2407032