title: 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.affiliation: Department of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
authors.forename: Ewa D
authors.initials: ED
authors.lastname: Micewicz
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, University Road, Leicester, LE1 9HN, UK.
authors.forename: Omar S O
authors.initials: OS
authors.lastname: Bahattab
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, University Road, Leicester, LE1 9HN, UK.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Willars
authors.affiliation: Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA; Department of Physiology and Biophysics, University of California Irvine, 1001 Health Sciences Road, Irvine, CA 92697, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Waring
authors.affiliation: Department of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024, USA; The Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, Los Angeles, CA 90024, USA.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Whitelegge
authors.affiliation: Department of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: McBride
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024, USA; The Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, Los Angeles, CA 90024, USA. Electronic address: pruchala@mednet.ucla.edu.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ruchala
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009479:Neuropeptides / Q000737:chemistry* / Q000494:pharmacology*; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019440:Anti-Obesity Agents; D004041:Dietary Fats; D009479:Neuropeptides; D054852:Small Molecule Libraries; C056900:neuromedin U; D002118:Calcium
keywords: Antiobesity agents; Lipid-conjugated peptides; Neuromedin U receptor agonists; Obesity