CL-387785

CL-387785 (EKI-785; WAY-EKI 785) is an orally active EGFR inhibitor with an IC₅₀ of 370 pM. CL-387785 inhibits EGF-stimulated EGFR autophosphorylation with an IC₅₀ of approximately 5 nM. CL-387,785 exerts selective inhibition on cell lines overexpressing EGFR or c-erbB-2, whereas it shows weak inhibitory effects on cell lines with low expression of these two receptors. CL-387785 effectively induces cell cycle arrest and apoptosis. CL-387785 can be used for the research of non-small cell lung cancer and autosomal recessive polycystic kidney disease^[1][2][3]. In Vitro:CL-387,785 (30-1000 nM; 3 days) induces G0/G1 cell cycle arrest in A431 and SK-BR-3 cells at concentrations of 300-1000 nM after 3 days of incubation, with minimal apoptosis at higher doses^[2].
CL-387,785 (0.1-30 μM; 48 h) inhibits the growth of gefitinib-resistant Ba/F3-EGFR^L858R-T790M cells with a cellular IC₅₀ of ~1 μmol/L^[3].
CL-387,785 (3 μM; 24 h) induces significant apoptosis in gefitinib-resistant Ba/F3-EGFR^L858R-T790M cells and sensitive Ba/F3-EGFR^L858R cells^[3].
CL-387,785 (0.3-10 μM; 6 h) inhibits phosphorylation of EGFR and its downstream signaling targets STAT5, AKT, and ERK 1/2 in gefitinib-resistant Ba/F3-EGFR^L858R-T790M cells with an IC₅₀ of ~1 μmol/L^[3].
CL-387,785 (0.1-3 μM; 6 h) completely inhibits phosphorylation of EGFR and its downstream signaling targets STAT5, AKT, and ERK 1/2 in gefitinib-resistant H1975 lung cancer cells^[3]. In Vivo:CL-387785 (25-100 mg/kg; intraperitoneal injection; once every 3 days; days 18-46) dose-dependently reduces collecting duct cyst formation, improves renal function, attenuates biliary abnormalities, and prolongs survival in autosomal recessive polycystic kidney disease mice^[1].
CL-387785 (20-80 mg/kg; i.p., p.o.; intermittent administration with repeated dosing for 10 consecutive days) inhibits the growth of EGF-R-overexpressing A431 tumors in nude mice, and the tumors respond to the repeated dosing regimen^[2].