Discovery of glycine sulfonamides as dual inhibitors of sn-1-diacylglycerol lipase ? and ?/?-hydrolase domain 6 (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Discovery of glycine sulfonamides as dual inhibitors of sn-1-diacylglycerol lipase ? and ?/?-hydrolase domain 6 (Articolo in rivista) (literal)

Anno

• 2014-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1021/jm500681z (literal)

Alternative label

• Janssen F.J.; Deng H.; Baggelaar M.P.; Allara M.; Van Der Wel T.; Den Dulk H.; Ligresti A.; Van Esbroeck A.C.M.; McGuire R.; Di Marzo V.; Overkleeft H.S.; Van Der Stelt M. (2014)
  Discovery of glycine sulfonamides as dual inhibitors of sn-1-diacylglycerol lipase ? and ?/?-hydrolase domain 6
  in Journal of medicinal chemistry (Online)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Janssen F.J.; Deng H.; Baggelaar M.P.; Allara M.; Van Der Wel T.; Den Dulk H.; Ligresti A.; Van Esbroeck A.C.M.; McGuire R.; Di Marzo V.; Overkleeft H.S.; Van Der Stelt M. (literal)

Pagina inizio

• 6610 (literal)

Pagina fine

• 6622 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

• http://www.scopus.com/inward/record.url?eid=2-s2.0-84906091270&partnerID=q2rCbXpz (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 57 (literal)

Rivista

• Journal of medicinal chemistry (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 15 (literal)

Note

• Scopu (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Department of Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, Netherlands; Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche 80078 Pozzuoli, Napoli, Italy; Bioaxis Research, 5351 SL Berghem, Netherlands (literal)

Titolo

• Discovery of glycine sulfonamides as dual inhibitors of sn-1-diacylglycerol lipase ? and ?/?-hydrolase domain 6 (literal)

Abstract

• sn-1-Diacylglycerol lipase ? (DAGL-?) is the main enzyme responsible for the production of the endocannabinoid 2-arachidonoylglycerol in the central nervous system. Glycine sulfonamides have recently been identified by a high throughput screening campaign as a novel class of inhibitors for this enzyme. Here, we report on the first structure-activity relationship study of glycine sulfonamide inhibitors and their brain membrane proteome-wide selectivity on serine hydrolases with activity-based protein profiling (ABPP). We found that (i) DAGL-? tolerates a variety of biaryl substituents, (ii) the sulfonamide is required for inducing a specific orientation of the 2,2-dimethylchroman substituent, and (iii) a carboxylic acid is essential for its activity. ABPP revealed that the sulfonamide glycine inhibitors have at least three off-targets, including ?/?-hydrolase domain 6 (ABHD6). Finally, we identified LEI-106 as a potent, dual DAGL-?/ABHD6 inhibitor, which makes this compound a potential lead for the discovery of new molecular therapies for diet-induced obesity and metabolic syndrome. © 2014 American Chemical Society. (literal)

Prodotto di

• Institute of biomolecular chemistry (ICB) (Istituto)
• Struttura, funzione e \"profiling\" di endocannabinoidi e ammidi bioattive di acidi grassi implicati nelle patologie umane (PM.P01.012.001) (Modulo)

Autore CNR

• ALESSIA LIGRESTI (Unità di personale interno)

Incoming links:

Autore CNR di

• ALESSIA LIGRESTI (Unità di personale interno)

Prodotto

• Institute of biomolecular chemistry (ICB) (Istituto)
• Struttura, funzione e \"profiling\" di endocannabinoidi e ammidi bioattive di acidi grassi implicati nelle patologie umane (PM.P01.012.001) (Modulo)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Journal of medicinal chemistry (Rivista)