tcsc3722 Telatinib

Telatinib (Bay 57-9352) is an orally active, small molecule inhibitor of VEGFR2, VEGFR3, PDGFα, and c-Kit with IC₅₀s of 6, 4, 15 and 1 nM, respectively.

IC50 & Target: IC50: 6 nM (VEGFR2), 4 nM (VEGFR3), 15 nM (PDGFα), 1 nM (c-Kit)^[1]

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^[2]. 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^[3]. 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^[4].

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^[1]. 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^[4].