Biological Activity
compound 56, 4-[(3-bromophenyl)amino]-6,7-diethoxyquinazoline, is a potent and specific inhibitor of the tyrosine kinase of the epidermal growth factor receptor (egfr) showing an ic50 of 0.006 nm. it competitively binds at the adenosine-triphosphate (atp) site of egfr. compound 56 is capable of inhibiting the phosphorylation of egf-dependent egfr, suppressing the proliferation and clonogenicity of a wide panel of egfr-overexpressing human cancer lines, and blocking egf-mediated mitogenesis and oncogenic transformation in fibroblasts overexpressing egfr. besides inhibiting egfr tyrosine kinase, it also inhibits the tyrosine kinase of human epidermal growth factor receptor 2 (her2/neu) but with a less potency.bridges aj, zhou h, cody dr, rewcastle gw, mcmichael a, showalter hd, fry dw, kraker aj, and denny wa. tyrosine kinase inhibitors. 8. an unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (pd 153035), a potent inhibitor of the epidermal growth factor receptor.j med chem 1966; 39 (1): 267-276monique bos, jhn mendelsohn, young-mee kim, joan albanell, david w. fry, and jose baelga. pd153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent manner. clin cancer res 1997;3:2099-2106
