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To develop potential PET tracers for imaging MAGL, we synthesized compound\n                    <jats:bold>36<\/jats:bold>\n                    as a reference compound. Surprisingly, we observed a significant discrepancy between the reported potency and our findings in two well\u2010established in vitro assays. Compound\n                    <jats:bold>36<\/jats:bold>\n                    exhibited no inhibition of endocannabinoid hydrolysis in HEK293 lysates overexpressing human MAGL in a glycerol\u2010based assay at 1\u2009\u03bcM. In the competitive ABPP assay, it appeared completely inactive inhibiting MAGL in mouse whole\u2010brain proteome even at 100\u2009\u03bcM. In addition, eight structural analogs (\n                    <jats:bold>2<\/jats:bold>\n                    \u2013\n                    <jats:bold>9<\/jats:bold>\n                    ) of compound\n                    <jats:bold>36<\/jats:bold>\n                    also failed to show any significant MAGL inhibition. Interestingly, when the synthetic substrate 4\u2010nitrophenyl acetate, also used by Zhi et al., was employed, compound\n                    <jats:bold>36<\/jats:bold>\n                    inhibited MAGL more effectively than in glycerol\u2010based assay, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 143\u2009nM, being almost 10\u2010fold less potent than reported. In our reversibility assay, compound\n                    <jats:bold>36<\/jats:bold>\n                    exhibited measurable MAGL inhibition only at a concentration of 100\u2009\u03bcM. In summary, this study contradicts the earlier report and therefore, compound\n                    <jats:bold>36<\/jats:bold>\n                    should be used with caution as a research tool in studies exploring MAGL inhibition.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70525","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:34:33Z","timestamp":1791182073000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discrepancy in Reported and Observed Monoacylglycerol Lipase Inhibition of Aryl Formyl Piperidine Containing Potent and Highly Selective Monoacylglycerol Lipase Inhibitor"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1301-9064","authenticated-orcid":false,"given":"Juha R.","family":"Savinainen","sequence":"first","affiliation":[{"name":"Institute of Biomedicine, School of Medicine, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9832-487X","authenticated-orcid":false,"given":"Praveen Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-7653","authenticated-orcid":false,"given":"Jari","family":"Yli\u2010Kauhaluoma","sequence":"additional","affiliation":[{"name":"Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2562-1888","authenticated-orcid":false,"given":"Jayendra Z.","family":"Patel","sequence":"additional","affiliation":[{"name":"Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy University of Helsinki  Helsinki 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