Details

Autor(en) / Beteiligte

• Hernández-Torres, Gloria
• Cipriano, Mariateresa
• Hedén, Erika
• Björklund, Emmelie
• Canales, Ángeles
• Zian, Debora
• Feliú, Ana
• Mecha, Miriam
• Guaza, Carmen
• Fowler, Christopher J.
• Ortega-Gutiérrez, Silvia
• López-Rodríguez, María L.

Titel

A Reversible and Selective Inhibitor of Monoacylglycerol Lipase Ameliorates Multiple Sclerosis

Ist Teil von

• Angewandte Chemie (International ed.), 2014-12, Vol.53 (50), p.13765-13770

Auflage

International ed. in English

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Monoacylglycerol lipase (MAGL) is the enzyme responsible for the inactivation of the endocannabinoid 2‐arachidonoylglycerol (2‐AG). MAGL inhibitors show analgesic and tissue‐protecting effects in several disease models. However, the few efficient and selective MAGL inhibitors described to date block the enzyme irreversibly, and this can lead to pharmacological tolerance. Hence, additional classes of MAGL inhibitors are needed to validate this enzyme as a therapeutic target. Here we report a potent, selective, and reversible MAGL inhibitor (IC50=0.18 μM) which is active in vivo and ameliorates the clinical progression of a multiple sclerosis (MS) mouse model without inducing undesirable CB1‐mediated side effects. These results support the interest in MAGL as a target for the treatment of MS. Reversibility is the key: The development of a potent, reversible, selective and in vivo active inhibitor of monoacylglycerol lipase (MAGL), the enzyme responsible for the inactivation of the endocannabinoid 2‐arachidonoylglycerol (2‐AG), validates, for the first time, the therapeutic potential of MAGL for the treatment of multiple sclerosis.