{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"KWKZCGMJGHHOKJ-ZKWNWVNESA-N","prefName":"Methoxy arachidonyl fluorophosphonate","symbol":"MAFP","iupacName":"(5Z,8Z,11Z,14Z)-1-[fluoro(méthoxy)phosphoryl]icosa-5,8,11,14-tétraène","aliases":["MAFP","methyl arachidonyl fluorophosphonate","méthyl arachidonyl fluorophosphonate","arachidonyl méthylfluorophosphonate"],"cas":null,"pubchemCid":"10429254","chebiId":null,"smiles":"CCCCC/C=C\\C/C=C\\C/C=C\\C/C=C\\CCCCP(=O)(OC)F","molecularFormula":"C21H36FO2P","molecularWeight":370.5,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/10429254"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"Organophosphoré à chaîne polyinsaturée. La molécule reprend intégralement le squelette arachidonique, vingt carbones et quatre doubles liaisons de configuration Z aux positions 5, 8, 11 et 14, motif partagé par l'anandamide et le 2-arachidonoylglycérol. Au lieu de la fonction amide ou ester de ces endocannabinoïdes, elle porte un fluorophosphonate méthylé, groupement électrophile de la même famille chimique que les insecticides organophosphorés et les inhibiteurs de cholinestérases. C'est ce couple motif de reconnaissance et tête réactive qui définit la classe des inhibiteurs covalents dirigés par le substrat."},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"An entirely chemical route, described here by class only. The molecule combines the arachidonic chain of twenty carbons and four double bonds, recognised by the enzymes that handle endocannabinoids, with a methylated fluorophosphonate group that constitutes the reactive head. That architecture illustrates a classical strategy of inhibitor design: grafting an electrophile onto the recognition motif of the natural substrate.","originNote":"A wholly synthetic compound with no natural occurrence. It is produced as a biochemical research reagent and has no human or veterinary use.","discovered":"Décrit en 1997 par Deutsch et collaborateurs, à l'université d'État de New York à Stony Brook, comme le premier inhibiteur irréversible puissant et relativement sélectif de l'enzyme qui hydrolyse l'anandamide. Il arrive à un moment où le champ manquait d'outils capables de bloquer durablement cette dégradation, condition nécessaire pour établir le rôle physiologique de l'endocannabinoïde lui-même."},"pharmacology":{"summaryFr":"Methoxy arachidonyl fluorophosphonate is an organophosphorus compound designed on a simple principle: carrying a reactive head on a motif that the target enzyme recognises as its substrate. The arachidonic chain ensures recognition by fatty acid amide hydrolase, and the fluorophosphonate phosphorylates the catalytic serine residue, which inactivates the enzyme irreversibly. Deutsch and colleagues established in 1997 that this combination made it about 800 times more potent than the reversible inhibitors then available on rat brain homogenates, and about a thousand times on intact cells, with a selectivity of three to four orders of magnitude with respect to chymotrypsin and trypsin. It was thus the first tool allowing the degradation of anandamide to be durably suppressed, a step without which the physiological role of that endocannabinoid remained difficult to establish. The same publication nevertheless flagged the decisive limitation of the compound: it also binds the CB1 receptor, which it occupies irreversibly with a median inhibitory concentration of 20 nanomolar, a value better than that of anandamide itself. A tool meant to measure the effect of an elevation of anandamide therefore acts simultaneously on the target of that same anandamide, which makes the interpretation of any result obtained with it delicate. The subsequent literature confirmed that arachidonic fluorophosphonates in fact inhibit a broad set of serine hydrolases, including the cytosolic phospholipases A2. The compound remains in use as a broad biochemical reagent, but it has been superseded as a selective tool by the inhibitors of the following generation, such as URB597.","receptorSummaryFr":"An irreversible inhibitor of fatty acid amide hydrolase, the enzyme responsible for the hydrolysis of anandamide. Deutsch and colleagues found it about 800 times more potent than arachidonyl trifluoromethyl ketone and than phenylmethanesulfonyl fluoride on rat brain homogenates, and about a thousand times more potent on intact neuroblastoma cells. Its relative selectivity was quantified by comparison with two classical proteases: it is about 3 000 times more potent at the amide hydrolase than at chymotrypsin, and about 30 000 times more than at trypsin. The compound moreover possesses a second property that complicates its use: it displaces the binding of the radioligand CP-55940 at the CB1 receptor with a median inhibitory concentration of 20 nanomolar, against 40 nanomolar for anandamide, and it binds there irreversibly, preventing any subsequent binding of the radioligand.","binding":[{"target":"FAAH","efficacy":"antagonist","relativeActivity":92,"reported":"Inhibition irréversible ; environ 800 fois plus puissante que l'arachidonyl trifluorométhylcétone","confidence":"medium"},{"target":"CB1","efficacy":"antagonist","relativeActivity":70,"reported":"IC50 = 20 nM en déplacement du [3H]CP-55940 ; liaison irréversible","confidence":"medium"}],"references":[{"label":"Deutsch et coll. 1997 : le MAFP, inhibiteur irréversible puissant de l'amidase de l'anandamide","pmid":"9065728","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/9065728/"}]},"pharmacokinetics":"Aucune donnée de pharmacocinétique n'est publiée, ni chez l'animal ni chez l'humain. Le composé est employé in vitro sur homogénats, préparations membranaires et cultures cellulaires. Aucune dose humaine n'est caractérisée et rien n'autorise à en extrapoler une.","metabolism":"Aucune étude de métabolisme n'est publiée. La réactivité électrophile du fluorophosphonate, qui n'est pas restreinte à l'amidohydrolase, conduit à une consommation de la molécule par l'ensemble des hydrolases à sérine accessibles et par les nucléophiles biologiques, ce qui rendrait attendue une disparition rapide dans un organisme entier sans que cela ait fait l'objet d'une mesure publiée.","detection":"La molécule ne figure dans aucun panel de dépistage et n'a pas d'intérêt médicolégal. Son usage se trace en laboratoire par les techniques de profilage d'activité des hydrolases à sérine, qui mesurent l'occupation des sites actifs plutôt que la molécule elle-même.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":10},{"key":"focus","label":"Clarity","description":"Sustained attention and clear thinking; functional lucidity, not euphoria.","intensity":5},{"key":"sleep","label":"Sleep","description":"Sedative effect: aids sleep onset and the continuity of deep sleep.","intensity":10},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":10},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":5}],"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'est disponible et aucune dose humaine n'est caractérisée. Le composé appartient chimiquement à la famille des organophosphorés, dont la toxicité repose sur l'inhibition d'hydrolases à sérine, et sa manipulation relève des précautions applicables à cette classe. La promiscuité de cible établie dans la littérature, qui s'étend aux phospholipases A2 cytosoliques et à d'autres hydrolases, est à la fois sa limite scientifique et la source de son risque."},"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":"Réactif de recherche ; 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":"Deutsch et coll. 1997 : le MAFP, inhibiteur irréversible puissant de l'amidase de l'anandamide","pmid":"9065728","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/9065728/"}],"meta":{"slug":"mafp","url":"https://en.phytogrammes.com/wiki/mafp","lastVerified":"2026-05-01","dataUpdatedAt":"2026-08-16","confidence":"medium","dataCompletenessPct":90,"disclaimerFr":"Contenu éditorial informatif, sans valeur d'avis médical ni juridique. Sources primaires citées par fiche. Réservé aux adultes."}}