CL-387785 blocks EGF-stimulated autoposphorylation of the receptor in cells (IC50, 5 nM), In cell lines that overexpress EGF-R or c-erbB-2, CL-387785 inhibits cell proliferation (IC50, 31 nM) primarily in a cytostatic manner.
In vivo
In nude mice overexpressed EGF-R, CL-387785 (80 mg/kg/day, p.o.) profoundly blocks the growth of tumor. In murine models of autosomal recessive polycystic kidney disease (ARPKD), treatment of Balb/c-bpk/bpk (BPK) mice with CL-387785 (90 mg/kg, i.p.) results in a marked reduction of collecting tubule cystic lesions, improved renal function, decreased biliary epithelial abnormalities, and prolonged life span. Doses of CL-387785 as low as 25 mg/kg reduces the growth of HCA-7-induced xenograft tumor, and a dose of 100 mg/kg prevents tumor growth entirely. Dose of 50 mg/kg CL-387785 is effective at reducing the growth of HCT-116-induced xenograft tumor.