{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"GFWNGVKCDGYFKG-UHFFFAOYSA-N","prefName":"URB754","symbol":"URB754","iupacName":"6-methyl-2-(4-methylanilino)-3,1-benzoxazin-4-one","aliases":["URB 754","URB-754"],"cas":"86672-58-4","pubchemCid":"848487","chebiId":null,"smiles":"CC1=CC=C(C=C1)NC2=NC3=C(C=C(C=C3)C)C(=O)O2","molecularFormula":"C16H14N2O2","molecularWeight":266.106,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/848487"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"Benzoxazinone, plus précisément une 6-méthyl-2-anilino-3,1-benzoxazin-4-one. Ce squelette est un motif classique d'inhibiteur de sérine hydrolases, le cycle oxazinone pouvant s'ouvrir au contact de la sérine catalytique, ce qui rendait chimiquement plausible l'activité initialement attribuée et explique en partie pourquoi l'erreur a été acceptée. La démonstration ultérieure a montré que cette plausibilité structurale ne se traduisait pas en activité mesurable sur les enzymes des endocannabinoïdes."},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"An entirely chemical route, described here by class only. The molecule is a benzoxazinone: a 3,1-benzoxazin-4-one core bears a methyl on the aromatic ring and an anilino function substituted by a methylphenyl. That skeleton is classically associated with the inhibition of serine hydrolases, which initially made the activity attributed to it plausible.","originNote":"A wholly synthetic compound with no natural occurrence. It has never had any use other than in the laboratory, and the activity that had earned it its interest did not belong to it.","discovered":"Identifié en 2005 par criblage d'une chimiothèque commerciale comme inhibiteur puissant de la lipase des monoacylglycérols, et publié à ce titre par Makara et collaborateurs dans Nature Neuroscience. Cette attribution s'est révélée fausse. Saario et collaborateurs, à l'université de Kuopio, n'ont retrouvé aucune activité en 2006, et Tarzia et collaborateurs ont établi en 2007 que l'activité observée provenait d'une impureté du lot commercial."},"pharmacology":{"summaryFr":"URB754 is interesting for what it is not. Published in 2005 in Nature Neuroscience as an inhibitor of monoacylglycerol lipase, arising from the screening of a commercial chemical library, it answered a real need in a field that then lacked tools for manipulating 2-arachidonoylglycerol concentrations. The correction came in two stages. In 2006 Saario and colleagues, at the University of Kuopio, report in Chemistry and Biology that they find no activity: no inhibition of 2-arachidonoylglycerol hydrolysis in rat brain, no inhibition of fatty acid amide hydrolase, no ability to reveal 2-arachidonoylglycerol signalling on sections, where a reference inhibitor succeeds without difficulty. Their conclusion is blunt: the compound cannot serve as a lead structure for developing inhibitors of that enzyme. In 2007 the group that had made the original publication itself identified the cause of the error. Analysis of the commercial lot by chromatography coupled to mass spectrometry and by nuclear magnetic resonance revealed an organomercurial impurity, bis(methylthio)mercurane, whose median inhibitory concentration at the enzyme is 11.9 nanomolar: it was this, and not the benzoxazinone, that carried all the observed activity. The 2005 work was the subject of an erratum published in Nature Neuroscience in 2007. The episode has a general and lasting reach: the apparent potency of a compound arising from a screen on commercial material is worth only as much as the purity of the lot, and attributing an activity to a structure requires that traces have been ruled out.","receptorSummaryFr":"No established activity on the endocannabinoid-degrading enzymes. The inhibition of monoacylglycerol lipase attributed to it in 2005 was not reproduced: Saario and colleagues report in 2006 that the compound inhibits neither the hydrolysis of 2-arachidonoylglycerol in rat brain preparations nor fatty acid amide hydrolase, and that it does not make it possible to reveal G protein activation by 2-arachidonoylglycerol on brain sections, where a reference inhibitor succeeds. Tarzia and colleagues identified the cause in 2007: the activity measured on the commercial lot came from an organomercurial impurity, bis(methylthio)mercurane, a very potent inhibitor of the enzyme with a median inhibitory concentration of 11.9 nanomolar, but unusable in biology owing to its toxicity and target promiscuity. The compound has no described action on cannabinoid receptors.","binding":[{"target":"MAGL","efficacy":"modulator","relativeActivity":3,"reported":"Aucune inhibition retrouvée ; l'activité initialement rapportée revenait à une impureté organomercurielle (Saario 2006 ; Tarzia 2007)","confidence":"medium"},{"target":"FAAH","efficacy":"modulator","relativeActivity":3,"reported":"Activité cérébrale résistante au composé (Saario et coll. 2006)","confidence":"medium"}],"references":[{"label":"Saario et coll. 2006 : l'URB754 n'a aucun effet sur l'hydrolyse ni sur la capacité de signalisation du 2-AG dans le cerveau de rat","pmid":"16931330","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/16931330/"},{"label":"Tarzia et coll. 2007 : identification d'une impureté bioactive dans un échantillon commercial d'URB754","pmid":"17970304","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/17970304/"},{"label":"Makara et coll. 2005 : attribution initiale de l'activité, corrigée par un erratum publié en 2007","pmid":"16116451","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/16116451/"}]},"pharmacokinetics":"Sans objet en pratique : le composé n'ayant pas d'activité établie sur ses cibles supposées, aucune étude de pharmacocinétique n'a de raison d'être et aucune n'est publiée. Aucune donnée humaine n'existe et aucune dose humaine n'est caractérisée.","metabolism":"Aucune étude de métabolisme n'est publiée pour ce composé. Le cycle benzoxazinone est chimiquement sensible à l'hydrolyse, propriété générale du motif plutôt que résultat mesuré pour cette molécule.","detection":"La molécule ne figure dans aucun panel de dépistage et n'a pas d'intérêt médicolégal. La leçon analytique de son histoire porte ailleurs : le contrôle de pureté d'un réactif par chromatographie couplée à la spectrométrie de masse et par résonance magnétique nucléaire fait partie intégrante de la validation d'un résultat pharmacologique.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":3},{"key":"focus","label":"Clarity","description":"Sustained attention and clear thinking; functional lucidity, not euphoria.","intensity":3},{"key":"sleep","label":"Sleep","description":"Sedative effect: aids sleep onset and the continuity of deep sleep.","intensity":3},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":3},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":3}],"doseRanges":null,"humanDataCharacterised":false},"indications":{"approvedMedicines":[]},"harmProfile":{"unstudiedBanner":true,"bannerTextFr":"Aucune dose humaine caractérisée : données animales / in vitro uniquement. Profil d'effet, marge de sécurité et toxicité aiguë non documentés en clinique humaine.","toxicologyFr":"Aucune donnée de toxicologie humaine n'existe et aucune dose humaine n'est caractérisée. Le risque documenté ne tient pas à la molécule mais à ce qui l'accompagnait : le bis(méthylthio)mercurane identifié dans le lot commercial est un composé organomercuriel dont l'usage biologique est proscrit en raison de sa toxicité et de son absence de sélectivité. Les auteurs de 2007 signalent explicitement ce point. Toute manipulation d'un lot ancien devrait en tenir compte."},"legal":{"scheduleStatus":"unscheduled","scheduleLabel":"Unscheduled","frScheduleStatus":"unscheduled","tiers":[{"jurisdiction":"international","jurisdictionLabel":"International","label":"Non inscrit aux conventions de contrôle","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"eu","jurisdictionLabel":"Union européenne","label":"Produit chimique de laboratoire ; non contrôlé","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"fr","jurisdictionLabel":"France","label":"Non inscrit ; usage de laboratoire uniquement","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null}],"sourcesFr":"EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA."},"references":[{"label":"Saario et coll. 2006 : l'URB754 n'a aucun effet sur l'hydrolyse ni sur la capacité de signalisation du 2-AG dans le cerveau de rat","pmid":"16931330","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/16931330/"},{"label":"Tarzia et coll. 2007 : identification d'une impureté bioactive dans un échantillon commercial d'URB754","pmid":"17970304","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/17970304/"},{"label":"Makara et coll. 2005 : attribution initiale de l'activité, corrigée par un erratum publié en 2007","pmid":"16116451","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/16116451/"}],"meta":{"slug":"urb754","url":"https://en.phytogrammes.com/wiki/urb754","lastVerified":"2026-05-01","dataUpdatedAt":"2026-08-17","confidence":"high","dataCompletenessPct":90,"disclaimerFr":"Contenu éditorial informatif, sans valeur d'avis médical ni juridique. Sources primaires citées par fiche. Réservé aux adultes."}}