CO-1686

Brand

No Brand

Description

CO-1686 (also know as AVL-301) is an orally available small molecule, irreversible inhibitor of epidermal growth factor receptor (EGFR) with potential antineoplastic activity. CO-1686 selectively inhibits proliferation in the mutant-EGFR NSCLC cells with GI50 ranging from 7 to 32 nM, and induces apoptosis. In NSCLC cells with acquired resistance to CO-1686 in vitro, there was no evidence of additional mutations or amplification of the EGFR gene, but resistant cells exhibited signs of epithelial-mesenchymal transition and demonstrated increased sensitivity to AKT inhibitors. In vivo, CO-1686 caused dose-dependent and significant tumor growth inhibition in all EGFR-mutant models as well as human EGFRL858R- and EGFRL858R/T790M-expressing transgenic mice. CO-1686 is approximately 22-fold selective over WT EGFR (kinactt/Ki = (1.12 ± 0.14) x 104 M-1s-1).

Application

Reactivity

Photos