Terry W. Moody, Nicole Tashakkori, Samuel A. Mantey, Paola Moreno, Irene Ramos-Alvarez, Marcello Leopoldo, Robert T. Jensen
Abstract
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 Ca(2+) 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.
Pharmacology, Toxicology and Pharmaceutical Science
3
25%
Biochemistry, Genetics and Molecular Biology
2
17%
Medicine and Dentistry
2
17%
Agricultural and Biological Sciences
1
8%
Veterinary Science and Veterinary Medicine
1
8%
Other
2
17%
Unknown
1
8%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 July 2017.
All research outputs
#23,269,088
of 25,932,719 outputs
Outputs from Frontiers in endocrinology
#8,555
of 13,317 outputs
Outputs of similar age
#289,175
of 329,092 outputs
Outputs of similar age from Frontiers in endocrinology
#74
of 100 outputs
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