Telatinib

An orally active, small molecule inhibitor of VEGFR-2 (IC50=6 nM), VEGFR-3 (IC50=4 nM), PDEGFRα (IC50=15 nM) and c-Kit (IC50=1 nM) in biochemical assays.Gastric Cancer Phase 2 Clinical (In Vitro) :Telatinib has low affinity for the Raf kinase pathway, epidermal growth factor receptor family, the fibroblast growth factor receptor (FGFR) family, or the Tie-2 receptor. Telatinib is metabolized by various cytochrome P450 (CYP) isoforms including CYP3A4/3A5, CYP2C8, CYP2C9, and CYP2C19 as well as by uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4), with the formation of the N-glucuronides of telatinib as the major biotransformation pathway in man. In vitro studies show telatinib to be a weak substrate of the adenosine triphosphate binding cassette (ABC) B1 (ABCB1) transporter. Telatinib at 1 μM significantly enhances the intracellular accumulation of [3H]-mitoxantrone (MX) in ABCG2-overexpressing cell lines. In addition, telatinib at 1 μM significantly reduces the rate of [3H]-MX efflux from ABCG2-overexpressing cells. Furthermore, telatinib significantly inhibits ABCG2-mediated transport of [3H]-E217βG in ABCG2 overexpressing membrane vesicles. (In Vivo) :Telatinib causes a significant decrease in endothelium-dependent and endothelium-independent vasodilation. VEGF inhibition by itself decreases NO synthesis, which promotes vasoconstriction, increases peripheral resistance, and therefore can induce an increase in blood pressure. Telatinib (15 mg/kg) with doxorubicin (1.8 mg/kg) significantly decreases the growth rate and tumor size of ABCG2 overexpressing tumors in a xenograft nude mouse model.

332012-40-5

Bay 57-9352

>98% (HPLC)

DMSO: ≥ 46 mg/mL

O=C (C1=NC=CC (COC2=NN=C (NC3=CC=C (Cl) C=C3) C4=C2OC=C4) =C1) NC

C20H16ClN5O3

409.8257

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.