Photo from wikipedia
Monoacylglycerol lipase (MAGL), a serine hydrolase extensively expressed throughout the brain, serves as a key gatekeeper regulating the tone of endocannabinoid signaling. Pre-clinically, inhibition of MAGL is known to provide… Click to show full abstract
Monoacylglycerol lipase (MAGL), a serine hydrolase extensively expressed throughout the brain, serves as a key gatekeeper regulating the tone of endocannabinoid signaling. Pre-clinically, inhibition of MAGL is known to provide therapeutic benefits for a number of neurological disorders. Availability of a MAGL-specific positron emission tomography (PET) ligand would considerably facilitate the development and clinical characterization of MAGL inhibitors via non-invasive and quantitative PET imaging. Herein, we report 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 rat, and non-human primate (NHP) PET imaging.
Journal Title: Journal of medicinal chemistry
Year Published: 2019
Link to full text (if available)
Share on Social Media: Sign Up to like & get
recommendations!