| Literature DB >> 31483137 |
Lei Zhang, Christopher R Butler, Kevin P Maresca, Akihiro Takano1, Sangram Nag1, Zhisheng Jia1, Ryosuke Arakawa1, Justin R Piro, Tarek Samad, Deborah L Smith, Deane M Nason, Steven O'Neil, Laura McAllister, Klaas Schildknegt, Patrick Trapa, Timothy J McCarthy, Anabella Villalobos, Christer Halldin1.
Abstract
Monoacylglycerol lipase (MAGL), a serine hydrolase extensively expressed throughout the brain, serves as a key gatekeeper regulating the tone of endocannabinoid signaling. Preclinically, inhibition of MAGL is known to provide therapeutic benefits for a number of neurological disorders. The availability of a MAGL-specific positron emission tomography (PET) ligand would considerably facilitate the development and clinical characterization of MAGL inhibitors via noninvasive and quantitative PET imaging. Herein, we report the identification of the potent and selective irreversible MAGL inhibitor 7 (PF-06809247) as a suitable radioligand lead, which upon radiolabeling was found to exhibit a high level of MAGL specificity; this enabled cross-species measurement of MAGL brain expression (Bmax), assessment of in vivo binding in the rat, and nonhuman primate PET imaging.Entities:
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Year: 2019 PMID： 31483137 DOI： 10.1021/acs.jmedchem.9b00847
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446