Small lipidated anti-obesity compounds derived from neuromedin U

Eur J Med Chem. 2015 Aug 28;101:616-26. doi: 10.1016/j.ejmech.2015.07.020. Epub 2015 Jul 14.

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.

Keywords: Antiobesity agents; Lipid-conjugated peptides; Neuromedin U receptor agonists; Obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Obesity Agents / chemical synthesis*
  • Anti-Obesity Agents / chemistry
  • Anti-Obesity Agents / 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*
  • Neuropeptides / pharmacology*
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Signal Transduction
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

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