Details

Autor(en) / Beteiligte

• Micewicz, Ewa D.
• Bahattab, Omar S.O.
• Willars, Gary B.
• Waring, Alan J.
• Navab, Mohamad
• Whitelegge, Julian P.
• McBride, William H.
• Ruchala, Piotr

Titel

Small lipidated anti-obesity compounds derived from neuromedin U

Ist Teil von

• European journal of medicinal chemistry, 2015-08, Vol.101, p.616-626

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Truncated analogs of neuromedin U are active in vivo.•Lipidated derivatives of NmU are viable drug candidates for obesity treatment.•Position of lipidation influences affinity of NmU derivatives to NMU1 and NMU2 receptors.•The pharmacokinetic properties of selected lipidated NmU derivatives were studied in murine model.