{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"OZEQTGDZTPJNAR-UHFFFAOYSA-N","prefName":"GAT100","symbol":"GAT100","iupacName":"[3-éthyl-2-[2-(4-pipéridin-1-ylphényl)éthylcarbamoyl]-1H-indol-5-yl] thiocyanate","aliases":["GAT-100","GAT 100"],"cas":null,"pubchemCid":"117923261","chebiId":null,"smiles":"CCC1=C(NC2=C1C=C(C=C2)SC#N)C(=O)NCCC3=CC=C(C=C3)N4CCCCC4","molecularFormula":"C25H28N4OS","molecularWeight":432.6,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/117923261"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"Modulateur allostérique covalent de la famille des indole-2-carboxamides, dérivé de l'Org27569. Le squelette conserve l'indole substitué par un éthyle en position 3 et le carboxamide en position 2, relié par une chaîne éthyle à un phényle portant une pipéridine. L'élément qui définit la molécule est le groupement électrophile porté par la position 5 de l'indole, qui lui permet de former une liaison covalente avec un résidu nucléophile du récepteur et donc de le marquer durablement. Cette architecture n'a aucun rapport avec celle des ligands orthostériques, ce qui est cohérent avec un site de liaison distinct."},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"An entirely chemical route, described here by class only. The molecule derives from the indole-2-carboxamide skeleton of Org27569, whose ethyl chain linked to a piperidine-substituted phenyl it retains. The decisive modification is the introduction of an isothiocyanate function on the indole core, an electrophilic group able to form a covalent bond with a residue of the receptor.","originNote":"A wholly synthetic compound with no natural occurrence. It is produced as a pharmacological probe for mapping the allosteric site of the CB1 receptor and has no clinical use.","discovered":"Issu d'une bibliothèque d'analogues covalents des deux modulateurs allostériques négatifs de référence du récepteur CB1, l'Org27569 et le PSNCBAM-1, conçue par l'équipe de Ganesh Thakur au Center for Drug Discovery. Les deux articles fondateurs paraissent en 2016 : le premier décrit la bibliothèque de sondes électrophiles et de photomarquage, le second isole ce composé comme chef de file et en dresse le profil de signalisation complet."},"pharmacology":{"summaryFr":"GAT100 is a covalent probe of the allosteric site of the CB1 receptor, designed to solve a precise methodological problem. The two historical negative allosteric modulators of that receptor, Org27569 and PSNCBAM-1, display an inverse agonism that blurs the interpretation of their effects: it is not always possible to separate what belongs to allosteric modulation proper from what belongs to a direct action on the constitutive activity of the receptor. Laprairie and colleagues screened a library of electrophilic and photoactivatable analogues of those two compounds and retained this one, bearing an isothiocyanate, as lead. The functional profile established across five downstream signalling pathways, beta-arrestin 1 recruitment, phosphorylation of phospholipase C beta 3 and of the ERK1/2 kinases, cyclic AMP accumulation and receptor internalisation, shows that it attenuates the response to the synthetic agonist CP55,940 as well as that of the two endocannabinoids, in three cellular systems two of which express the receptor endogenously. It proved more potent and more efficacious than its two models, and above all devoid of their inverse agonism in the labelled GTPγS assay. Its covalent nature, which fixes it durably to the receptor, makes it a marker usable for mapping the allosteric site itself, and docking simulations designate the cysteine 7.38(382) residue as anchor point. The practical stake is therapeutic in the longer run: modulating CB1 activity without activating or blocking it head-on would offer a route of access to that target without the adverse effects that caused orthosteric agonists and antagonists to fail.","receptorSummaryFr":"A covalent negative allosteric modulator of the CB1 receptor. The compound does not bind to the orthosteric site occupied by cannabinoids, but to a distinct site whose response it modifies. Laprairie and colleagues established that it reduces the effect of the orthosteric agonist CP55,940 as well as that of the endocannabinoids 2-arachidonoylglycerol and anandamide, on beta-arrestin 1 recruitment, phosphorylation of phospholipase C beta 3 and of the ERK1/2 kinases, cyclic AMP accumulation and receptor internalisation, in HEK293A cells overexpressing CB1 as in Neuro2a and STHdh cells expressing the receptor endogenously. Its peculiarity is that it is more potent and more efficacious than Org27569 and PSNCBAM-1 while being devoid of the inverse agonism those two display, which makes it a cleaner probe. Docking studies designate cysteine 7.38(382) as a key determinant of its binding.","binding":[{"target":"CB1 (site allostérique)","efficacy":"modulator","relativeActivity":80,"reported":"Modulateur allostérique négatif covalent ; déterminant clé C7.38(382)","confidence":"medium"},{"target":"CB1","efficacy":"modulator","relativeActivity":15,"reported":"Aucune action sur le site orthostérique ; pas d'agonisme inverse","confidence":"medium"}],"references":[{"label":"Laprairie et coll. 2016 : cartographie du site allostérique du CB1, déterminant moléculaire et profil de signalisation du GAT100","pmid":"27046127","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/27046127/"},{"label":"Kulkarni et coll. 2016 : sondes covalentes électrophiles et de photomarquage du site allostérique du récepteur CB1","pmid":"26529344","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/26529344/"}]},"pharmacokinetics":"Aucune donnée de pharmacocinétique n'est publiée, ni chez l'animal ni chez l'humain. Le composé est une sonde in vitro, employée sur cultures cellulaires et préparations membranaires. Aucune dose humaine n'est caractérisée.","metabolism":"Aucune étude de métabolisme n'est publiée. La fonction isothiocyanate, qui fait tout l'intérêt du composé, est aussi un groupement réactif vis-à-vis des thiols biologiques en général, notamment du glutathion, ce qui rendrait attendue une consommation rapide de la molécule dans un organisme entier, mais cette attente n'a pas fait l'objet d'une mesure publiée.","detection":"La molécule ne figure dans aucun panel de dépistage et n'a pas d'intérêt médicolégal. Sa détection relève des méthodes de protéomique chimique et de spectrométrie de masse employées pour identifier les résidus marqués par les sondes covalentes.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":5},{"key":"focus","label":"Clarity","description":"Sustained attention and clear thinking; functional lucidity, not euphoria.","intensity":20},{"key":"sleep","label":"Sleep","description":"Sedative effect: aids sleep onset and the continuity of deep sleep.","intensity":5},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":5},{"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 n'est disponible et aucune dose humaine n'est caractérisée. Le composé n'a jamais été administré à l'humain. Le caractère électrophile de sa fonction réactive, qui n'est pas sélective du récepteur CB1 dans l'absolu, constitue le point de vigilance attendu pour toute sonde covalente employée hors du contexte in vitro."},"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":"Sonde de recherche ; non contrôlée","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":"Laprairie et coll. 2016 : cartographie du site allostérique du CB1, déterminant moléculaire et profil de signalisation du GAT100","pmid":"27046127","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/27046127/"},{"label":"Kulkarni et coll. 2016 : sondes covalentes électrophiles et de photomarquage du site allostérique du récepteur CB1","pmid":"26529344","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/26529344/"}],"meta":{"slug":"gat100","url":"https://en.phytogrammes.com/wiki/gat100","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."}}