Telatinib is a multi-kinase inhibitor that inhibits VEGF receptor 2 (VEGFR2), VEGFR3, PDGFRα, and c-Kit (IC50s = 6, 4, 15, and 1 nM, respectively). It also binds to the transmembrane region of the ABCG2 efflux transporter and enhances intracellular accumulation of [3H]-mitoxantrone in ABCG2-overexpressing cells. Telatinib (15 mg/kg) decreases tumor growth rate and size in an H460/MX20 mouse xenograft model.
Telatinib small-molecule inhibitor of vascular endothelial growth factor receptors 2 and 3 (VEGFR-2/-3) and platelet-derived growth factor receptor β tyrosine kinases. Telatinib is used therapeutically in patients with advanced solid tumors.
Telatinib (BAY 57-9352) is an orally available, potent multitargeted VEGFR-2, VEGFR-3, PDGFR-β and c-Kit tyrosine kinases inhibitor with an IC50 of 19 nM for the inhibition of VEGFR-2 autophosphorylation.
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].
VEGFR2: 6 nM (IC50); VEGFR3: 4 nM (IC50); PDGFRα: 15 nM (IC50); c-Kit: 1 nM (IC50)
[1]. steeghs, n., et al., hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis inhibitor. clin cancer res, 2008. 14(11): p. 3470-6.
[2]. strumberg, d., et al., phase i dose escalation study of telatinib (bay 57-9352) in patients with advanced solid tumours. br j cancer, 2008. 99(10): p. 1579-85.
[3]. sodani, k., et al., telatinib reverses chemotherapeutic multidrug resistance mediated by abcg2 efflux transporter in vitro and in vivo. biochem pharmacol, 2014. 89(1): p. 52-61.
[4]. eskens, f.a., et al., phase i dose escalation study of telatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and 3, platelet-derived growth factor receptor beta, and c-kit, in patients with advanced or metastatic solid tumors. j clin oncol, 2009. 27(25): p. 4169-76.
