(2S)-3-(1H-INDOL-3-YL)-N-[[1-(5-METHOXYPYRIDIN-2-YL)CYCLOHEXYL]METHYL]-2-METHYL-2-[(4-NITROPHENYL)CARBAMOYLAMINO]PROPANAMIDE

Ki: 0.17 nM (Human BB ₁ receptor), 0.66 nM (Rat BB ₁ receptor), 1 nM (Human BB ₂ receptor), 16 nM (Rat BB ₂ receptor)
EC50: 0.31 μM (FPR1), 0.66 μM (FPR2)

PD176252 is a potent antagonist of neuromedin-B preferring (BB ₁ ) and gastrin-releasing peptide-preferring (BB ₂ ) receptor with K _i s of 0.17 nM and 1 nM for human BB ₁ and BB ₂ receptors, and 0.66 nM, 16 nM for Rat BB ₁ and BB ₂ receptors, respectively. PD176252 inhibits acidification responses to neuromedin-B or neuromedin-C at the human BB ₁ or BB ₂ receptors expressed in CHO cells, with the appK _B s of 4.0 nM or 13 nM, and blocks bombesin-evoked increases in intracellular calcium levels in CHO cells stably expressing human BB ₁ or BB ₂ receptors, with appK _B s of 2.3 nM and 36 nM, respectively. PD176252 is also an agonist of N-Formyl peptide receptor1/2 (FPR1/FPR2), with EC ₅₀ s of 0.31 and 0.66 μM in HL-60 cells. PD176252 activates Ca ²⁺ mobilization in HL-60 cells transfected with human FPRs (EC ₅₀ , 0.72 ± 0.21 μM). PD176252 inhibits little specific ¹²⁵ I-gastrin releasing peptide binding to NCI-H345 cells at 1 nM and suppresses almost all specific bindings at 1000 nM, with an IC ₅₀ of 30 nM. PD176252 (10, 30 μM) significantly inhibits the growth of NCI-H345 or H1299 cells, with IC ₅₀ s of 7 and 5 μM.

PD176252 (1, 10 μg, p.o.) potently inhibits the growth of the proliferation of NCI-H1299 xenografts in nude mice.