{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"RYNSGDFWBJWWSZ-UHFFFAOYSA-N","prefName":"LY-320135","symbol":"LY-320135","iupacName":"4-[[6-méthoxy-2-(4-méthoxyphényl)-1-benzofuran-3-yl]carbonyl]benzonitrile","aliases":["LY320135","LY 320135"],"cas":"176977-56-3","pubchemCid":"5311257","chebiId":null,"smiles":"COC1=CC=C(C=C1)C2=C(C3=C(O2)C=C(C=C3)OC)C(=O)C4=CC=C(C=C4)C#N","molecularFormula":"C24H17NO4","molecularWeight":383.4,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/5311257"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"Antagoniste CB1 à noyau benzofurane, chimiquement isolé parmi les ligands de ce récepteur. Le benzofurane porte un méthoxyphényle en position 2 et une cétone aromatique en position 3, laquelle relie le squelette à un benzonitrile. Cette architecture n'emprunte ni au diarylpyrazole du rimonabant ni au squelette benzo[c]chromène des cannabinoïdes végétaux, ce qui en faisait, selon les auteurs, une tête de série prometteuse pour développer des antagonistes de structure nouvelle."},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"An entirely chemical route, described here by class only. The molecule is built on a benzofuran core bearing an aromatic ketone function and a nitrile, a structure unrelated to the pyrazoles of the rimonabant lineage or to the classical cannabinoids. It is that originality of skeleton that the authors emphasised.","originNote":"A wholly synthetic compound with no natural occurrence. It is produced as a pharmacological research reagent and has never been the subject of clinical development.","discovered":"Décrit en 1998 par Felder et collaborateurs, dans un travail conduit entre les laboratoires Eli Lilly et l'Institut national américain de santé mentale. L'intérêt de la publication dépasse la molécule elle-même : c'est en l'utilisant que les auteurs ont mis en évidence un couplage du récepteur CB1 à la stimulation de l'adénylylcyclase, phénomène masqué en conditions ordinaires par la voie inhibitrice dominante."},"pharmacology":{"summaryFr":"LY-320135 is a CB1 receptor antagonist described in 1998 by Felder and colleagues, remarkable for its benzofuran skeleton, unrelated to the pyrazoles of the rimonabant lineage or to the classical cannabinoids. Its selectivity is clear: the inhibition constant stands at 224 nanomolar at the CB1 receptor expressed in a stable line, against more than 10 micromolar at CB2, a factor greater than seventy, and neighbouring values are found on cerebellum and spleen membranes. Its main interest is, however, methodological. By treating CB1-expressing cells with pertussis toxin, the authors neutralised the Gi and Go proteins that carry the inhibition of adenylyl cyclase by anandamide, and then saw a stimulatory effect of that same anandamide on the enzyme appear. The compound blocked that stimulatory component, which made it possible to attribute it unambiguously to the CB1 receptor rather than to a parallel target. That result helped establish that CB1 is not coupled to a single signalling pathway and that it can recruit Gs proteins depending on cellular context, a notion that today structures the reading of biased cannabinoid signalling. The compound moreover blocks the inhibition of N-type calcium channels and the activation of inwardly rectifying potassium channels produced by WIN 55212-2. It remained a pharmacological tool and was not developed further.","receptorSummaryFr":"A selective antagonist of the CB1 receptor. Felder and colleagues measured an inhibition constant of 224 nanomolar at the CB1 receptor stably expressed in a cell line, against more than 10 micromolar at CB2, that is a selectivity greater than seventy times. Concordant values were obtained on native membrane preparations, 203 nanomolar on cerebellum and more than 10 micromolar on spleen. Functionally, the compound reverses the inhibition of adenylyl cyclase produced by anandamide, blocks the inhibition of N-type calcium channels by WIN 55212-2 and prevents the activation of inwardly rectifying potassium channels.","binding":[{"target":"CB1","efficacy":"antagonist","relativeActivity":70,"reported":"Ki = 224 nM (lignée stable) ; 203 nM sur membranes de cervelet","confidence":"medium"},{"target":"CB2","efficacy":"modulator","relativeActivity":5,"reported":"Ki supérieur à 10 µM ; sélectivité CB1 supérieure à 70 fois","confidence":"medium"}],"references":[{"label":"Felder et coll. 1998 : le LY320135, antagoniste CB1 révélant le couplage du récepteur à la stimulation de l'AMP cyclique","pmid":"9435190","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/9435190/"}]},"pharmacokinetics":"Aucune donnée de pharmacocinétique humaine ou animale détaillée n'est publiée. Le composé n'a pas été développé comme médicament et son usage est resté cantonné aux préparations membranaires et aux cultures cellulaires. Aucune dose humaine n'est caractérisée.","metabolism":"Aucune étude de métabolisme n'est publiée pour ce composé. Sa structure comporte deux fonctions méthoxy et un nitrile, motifs habituellement sujets à déméthylation oxydative et à hydrolyse, mais aucune donnée mesurée ne permet de décrire son devenir dans un organisme.","detection":"La molécule ne figure dans aucun panel de dépistage et n'a pas d'intérêt médicolégal. Sa quantification relève des méthodes analytiques de laboratoire, par chromatographie liquide couplée à la spectrométrie de masse.","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":30},{"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":3},{"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 publiée et aucune dose humaine n'est caractérisée. Le composé n'a jamais été administré à l'humain. Les antagonistes du récepteur CB1 constituent par ailleurs une classe dont le risque psychiatrique a été établi avec le rimonabant, ce qui interdit toute extrapolation rassurante à partir de la seule absence de données."},"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":"Felder et coll. 1998 : le LY320135, antagoniste CB1 révélant le couplage du récepteur à la stimulation de l'AMP cyclique","pmid":"9435190","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/9435190/"}],"meta":{"slug":"ly-320135","url":"https://en.phytogrammes.com/wiki/ly-320135","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."}}