PD176252 is a potent BB1 and BB2 antagonist with inhibitory effects on BB1 and BB2 receptors.PD176252 acts as a small molecule GRPR inhibitor and FPR1/FPR2 agonist to inhibit the growth and proliferation of a variety of cancer cells.

FPR:0.72±0.21 μM (EC50, human), FPR2:0.66 μM (EC50), BB2 receptor:16 nM (Rat), BB2 receptor:1 nM (Ki, Human), BB1 receptor:0.66 nM (Ki, Rat), BB1 receptor:0.17 nM (Ki, Human), FPR1:0.31 μM (EC50)

PD176252 is a potent antagonist of neuromedin-B preferring (BB1) and gastrin-releasing peptide-preferring (BB2) receptors, with Kis of 0.17 nM and 1 nM for human BB1 and BB2, and 0.66 nM and 16 nM for rat BB1 and BB2 receptors, respectively. In CHO cells expressing human BB1 or BB2 receptors, PD176252 inhibits acidification responses to neuromedin-B or neuromedin-C with appKBs of 4.0 nM and 13 nM, respectively. It also blocks bombesin-evoked increases in intracellular calcium levels, with appKBs of 2.3 nM and 36 nM, respectively. Additionally, PD176252 is an agonist of N-Formyl peptide receptor1/2 (FPR1/FPR2), with EC50s of 0.31 and 0.66 μM in HL-60 cells, activating Ca2+ mobilization in HL-60 cells transfected with human FPRs (EC50, 0.72 ± 0.21 μM)[2]. PD176252 shows little specific 125I-gastrin releasing peptide binding to NCI-H345 cells at 1 nM but suppresses almost all specific binding at 1000 nM, with an IC50 of 30 nM. Furthermore, PD176252 (10, 30 μM) significantly inhibits the growth of NCI-H345 or H1299 cells, with IC50s of 7 and 5 μM[1].

Orally administered PD176252 (1, 10 μg) potently inhibits the growth and proliferation of NCI-H1299 xenografts in nude mice[1].