Small lipidated anti-obesity compounds derived from neuromedin U.

Abstract

A small library of truncated/lipid-conjugated neuromedin U (NmU) analogs was synthesized and tested in vitro using an intracellular calcium signaling assay. The selected, most active analogs were then tested in vivo, and showed potent anorexigenic effects in a diet-induced obese (DIO) mouse model. The most promising compound, NM4-C16 was effective in a once-weekly-dose regimen. Collectively, our findings suggest that short, lipidated analogs of NmU are suitable leads for the development of novel anti-obesity therapeutics.

• Authors: Ewa D Micewicz, Omar S O Bahattab, Gary B Willars, Alan J Waring, Mohamad Navab, Julian P Whitelegge, William H McBride, Piotr Ruchala
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 101 Pg. 616-26 (Aug 28 2015) ISSN: 1768-3254 [Electronic] France
• PMID: 26204509 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Chemical References

• Anti-Obesity Agents
• Dietary Fats
• Neuropeptides
• Small Molecule Libraries
• neuromedin U
• Calcium

Topics

• Animals
• Anti-Obesity Agents (chemical synthesis, chemistry, pharmacology)
• Calcium (metabolism)
• Dietary Fats (adverse effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• HEK293 Cells
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Molecular Structure
• Neuropeptides (chemistry, pharmacology)
• Obesity (drug therapy, metabolism)
• Signal Transduction
• Small Molecule Libraries (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship