Tesevatinib

Tesevatinib (XL-647) is an orally available, blood-brain barrier-penetrant inhibitor of the epidermal growth factor receptor (EGFR). Tesevatinib significantly reduces cellular viability, with IC₅₀ values of 11 nM and 102 nM in GBM12 and GBM6, respectively. Tesevatinib also inhibits HER2 (IC₅₀=16.1 nM), VEGFR2 (IC₅₀=1.5 nM), and Src (IC₅₀=10.3 nM). Tesevatinib can inhibit tumor proliferation and exhibits antitumor activity^[1][2]. IC50 & Target:IC50: 0.3 nM (EGFR), 16 nM (EGFR), 1.5 nM (EGFR), 8.7 nM (EGFR), 1.4 nM (EGFR)^[1] In Vitro: Tesevatinib (XL-647) potently inhibits the EGF/ErbB2, VEGF, and ephrin RTK families. Tesevatinib (XL-647) is a reversible and ATP competitive inhibitor. Tesevatinib (XL-647) was inactive against a panel of 10 tyrosine kinases (including the insulin and the insulin-like growth factor-1 receptor) and 55 serine-threonine kinases (including cyclin-dependent kinases, stress-activated protein kinases, and protein kinase C isoforms). Tesevatinib (XL-647) inhibits cellular proliferation and EGFR pathway activation in the erlotinib-resistant H1975 cell line that harbors a double mutation (L858R and T790M) in the EGFR gene. In A431 cells, Tesevatinib (XL-647) reduces cell viability with IC₅₀ values of 13 nM^[1]. In Vivo: Tesevatinib (XL-647) shows potent and long-lived inhibition of the WT EGFR in vivo. Tesevatinib (XL-647) substantially inhibits the growth of H1975 xenograft tumors and reduces both tumor EGFR signaling and tumor vessel density^[1].