CL-387785(EKI785; WAY-EKI 785) is an irreversible inhibitor of EGFR with IC50 of 370(addition)/-120 pM; is able to overcome resistance caused by the T790M.

CL-387785 blocked EGF-stimulated autophosphorylation of the receptor in cells (ic50 approximately 5 nM), inhibited cell proliferation (IC50 = 31-125 nM) primarily in a cytostatic manner in cell lines that overexpress EGF-R or c-erbB-2 [1]. Whereas transformation by most EGFR mutants confers on cells sensitivity to erlotinib and gefitinib, transformation by an exon 20 insertion makes cells resistant to these inhibitors but more sensitive to the irreversible inhibitor CL-387,785 [3]. CL-387,785 is able to overcome resistance caused by the T790M mutation on a functional level, correlating with effective inhibition of downstream signaling pathways.