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=Volume 8 - 2017

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=While peptide antagonists for the gastrin releasing peptide receptor (BB2R), neuromedin B receptor (BB1R) and bombesin receptor subtype-3 (BRS-3) exist, there is a need to develop nonpeptide small molecule inhibitors for all three BBR.  The bombesin 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 BB2R, BB1R and BRS-3 with similar affinity (Ki = 1.4-10.8 uM).  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 which have BBR.  The results indicated that AM-37 and ST-36 function as small molecule BBR antagonists.