The ability of nonpeptide antagonists to interact with gastrin releasing peptide receptors on @entity2 cells was investigated. PD176252 (3-(1H-Indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide) and PD168368 (3-(1H-Indol-3-yl)-2-methyl-2-[3(4-nitro-phenyl)-ureido]-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide) inhibited specific 125I-gastrin releasing peptide binding to @entity1 cells with IC50 values of 20 and 1500 nM, respectively. Similar binding results were obtained using NCI-H157, H345 and N592 @entity1 @entity2 cells. PD176252 inhibited the ability of 1 nM bombesin to cause elevation of cytosolic calcium in Fura-2 loaded @entity1 or H1299 cells, whereas it had no effect on basal cytosolic calcium. PD176252 antagonized the ability of 10 nM bombesin to cause elevation of @entity1639 mRNA in @entity1 cells. Also, PD176252 inhibited the ability of 100 nM bombesin to cause tyrosine phosphorylation of focal adhesion kinase in @entity1 cells. Using a [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay, PD176252 was more potent than PD168368 at inhibiting NCI-H1299 proliferation. Also, 1 microM PD176252 significantly inhibited @entity2 colony number in vitro. PD176252 in a dose-dependent manner inhibited NCI-H1299 xenograft growth in @entity19 in vivo. These results indicate that PD176252 is a gastrin releasing peptide receptor antagonist, which inhibits the proliferation of @entity2 cells.

Nonpeptide gastrin releasing peptide receptor antagonists inhibit the proliferation of XXXX cells.

@entity1 :: ('9606', 'Species') :: ['NCI-H345', 'human', 'NCI-H1299'] @entity19 :: ('10090', 'Species') :: ['nude mice'] @entity2 :: ('MESH:D008175', 'Disease') :: ['lung cancer'] @entity1639 :: ('2353', 'Gene') :: ['c-fos']
@entity2 :: (MESH:D008175,Disease) :: ['lung cancer']
