CNX2006 (CNX-2006) is a potent, covalent, mutant-selective EGFR inhibitor with IC50 of <20 nM, weak inhibition at wild-type EGFR.
CNX2006 inhibits the phosphorylation of EGFR-T790M alone or the T790M mutation in cis with activating mutations with IC50 of 46 and 61 nM in NSCLC cell lines NCI-H1975 and PC9GR4, respectively.
CNX-2006 affected the WT-EGFR only at concentrations 10-fold higher than the ones necessary to inhibit mutated receptor.
CNX-2006 is also active against rare EGFR mutations, including EGFR-G719S, -ex19ins (I744-K745insKIPVAI), -L861Q, -ex20ins (H773-V774HVdup), and -T854A.
CNX-2006 inhibits mutant-EGFR cell proliferation by inducing apoptosis in vitro. CNX-2006 inhibits EGFR-T790M tumor growth in vivo.
