Frontiers in Endocrinology (Jul 2017)

AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists

  • Terry W. Moody,
  • Nicole Tashakkori,
  • Samuel A. Mantey,
  • Paola Moreno,
  • Irene Ramos-Alvarez,
  • Marcello Leopoldo,
  • Robert T. Jensen

DOI
https://doi.org/10.3389/fendo.2017.00176
Journal volume & issue
Vol. 8

Abstract

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While peptide antagonists for the gastrin-releasing peptide receptor (BB2R), neuromedin B receptor (BB1R), and bombesin (BB) receptor subtype-3 (BRS-3) exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA)1 binds with high affinity to the BB1R, BB2R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB1R, BB2R, and BRS-3 with similar affinity (Ki = 1.4–10.8 µM). AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca2+ in human lung cancer cells transfected with BB1R, BB2R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists.

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