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

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

JOURNAL=Frontiers in Endocrinology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2017.00176

DOI=10.3389/fendo.2017.00176

ISSN=1664-2392

ABSTRACT=<p>While peptide antagonists for the gastrin-releasing peptide receptor (BB<sub>2</sub>R), neuromedin B receptor (BB<sub>1</sub>R), 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 BB<sub>1</sub>R, BB<sub>2</sub>R, 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 BB<sub>1</sub>R, BB<sub>2</sub>R, and BRS-3 with similar affinity (<italic>K</italic>i = 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 Ca<sup>2+</sup> in human lung cancer cells transfected with BB<sub>1</sub>R, BB<sub>2</sub>R, 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.</p>