Abstract

During the year the receptor pharmacology and molecular pharmacology of primarily of the bombesin receptor family (GRPR, NMBR, BRS-3) was investigated as well as publishing a number of expert opinions of advances in this field. The molecular basis of selectivity of a newly described antagonist for the orphan receptor, BRS-3 receptor, which is a member of the Bn family of receptors, Bantag-1, was determined and published, which should help in the design of future selective ligands for this receptor. Inn collaboration with Prof M Leopolo of the f Universit degli Studi di Bari Aldo Moro, Bari, Italy. a number of potential small molecule inhibitors of Bombesin receptors were screened. Two were discovered to function as BnR antagonists, AM-37 and ST-36. In the micro molar rage each of these inhibited BB1, BB2 and BB3 activation and may be useful as templates to develop more potent antagonistic analogues. In addition, the pharmacological selectivity of newly described chiral diazepine antagonists for the BRS-3 receptor over the closely related GRPR and NBMR was determined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADK053100-29
Application #
9555626
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
29
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Thomas, Komba; Moody, Terry W; Jensen, Robert T et al. (2018) Design, synthesis and biological evaluation of hybrid nitroxide-based non-steroidal anti-inflammatory drugs. Eur J Med Chem 147:34-47
Moreno, Paola; Mantey, Samuel A; Lee, Suk H et al. (2018) A possible new target in lung-cancer cells: The orphan receptor, bombesin receptor subtype-3. Peptides 101:213-226
Moody, Terry W; Tashakkori, Nicole; Mantey, Samuel A et al. (2017) AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists. Front Endocrinol (Lausanne) 8:176
Ramos-Álvarez, Irene; Nakamura, Taichi; Mantey, Samuel A et al. (2016) Novel chiral-diazepines function as specific, selective receptor agonists with variable coupling and species variability in human, mouse and rat BRS-3 receptor cells. Peptides 75:8-17
Moreno, Paola; Ramos-Álvarez, Irene; Moody, Terry W et al. (2016) Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment. Expert Opin Ther Targets 20:1055-73
Moody, Terry W; Nuche-Berenguer, Bernardo; Jensen, Robert T (2016) Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer. Curr Opin Endocrinol Diabetes Obes 23:38-47
Nakamura, Taichi; Ramos-Álvarez, Irene; Iordanskaia, Tatiana et al. (2016) Molecular basis for high affinity and selectivity of peptide antagonist, Bantag-1, for the orphan BB3 receptor. Biochem Pharmacol 115:64-76
González, Nieves; Moreno, Paola; Jensen, Robert T (2015) Bombesin receptor subtype 3 as a potential target for obesity and diabetes. Expert Opin Ther Targets 19:1153-70
Ramos-Álvarez, Irene; Moreno, Paola; Mantey, Samuel A et al. (2015) Insights into bombesin receptors and ligands: Highlighting recent advances. Peptides 72:128-44
Moody, Terry W; Nuche-Berenguer, Bernardo; Moreno, Paola et al. (2015) CI-988 Inhibits EGFR Transactivation and Proliferation Caused by Addition of CCK/Gastrin to Lung Cancer Cells. J Mol Neurosci 56:663-72

Showing the most recent 10 out of 27 publications