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dc.rights.licenseopenen_US
dc.contributor.authorMULLER, Tania
dc.contributor.authorDEMIZIEUX, Laurent
dc.contributor.authorTROY FIORAMONTI, Stephanie
dc.contributor.authorBUCH, Chloe
dc.contributor.authorLEEMPUT, Julia
hal.structure.identifierCentre des Sciences du Goût et de l'Alimentation [Dijon] [CSGA]
dc.contributor.authorBELLOIR, Christine
dc.contributor.authorDE BARROS, J.-P.P.
dc.contributor.authorJOURDAN, Tony
dc.contributor.authorPASSILLY DEGRACE, Patricia
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
hal.structure.identifierCentre des Sciences du Goût et de l'Alimentation [Dijon] [CSGA]
dc.contributor.authorFIORAMONTI, Xavier
dc.contributor.authorLE, Bon, A.-M.
dc.contributor.authorVERGÈS, B.
dc.contributor.authorROBERT, J.-M.
dc.contributor.authorDEGRACE, P.
dc.date.accessioned2023-03-09T11:15:20Z
dc.date.available2023-03-09T11:15:20Z
dc.date.issued2022-03-08
dc.identifier.issn1661-6596en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/172232
dc.description.abstractEnTargeting cannabinoid 1 receptors (CB1R) with peripherally restricted antagonists (or inverse agonists) shows promise to improve metabolic disorders associated with obesity. In this context, we designed and synthetized JM-00266, a new CB1R blocker with limited blood–brain barrier (BBB) permeability. Pharmacokinetics were tested with SwissADME and in vivo in rodents after oral and intraperitoneal administration of JM-00266 in comparison with Rimonabant. In silico predictions indicated JM-00266 is a non-brain penetrant compound and this was confirmed by brain/plasma ratios and brain uptake index values. JM-00266 had no impact on food intake, anxiety-related behavior and body temperature suggesting an absence of central activity. cAMP assays performed in CB1R-transfected HEK293T/17 cells showed that the drug exhibited inverse agonist activity on CB1R. In addition, JM-00266 counteracted anandamide-induced gastroparesis indicating substantial peripheral activity. Acute administration of JM-00266 also improved glucose tolerance and insulin sensitivity in wild-type mice, but not in CB1R−/− mice. Furthermore, the accumulation of JM-00266 in adipose tissue was associated with an increase in lipolysis. In conclusion, JM-00266 or derivatives can be predicted as a new candidate for modulating peripheral endocannabinoid activity and improving obesity-related metabolic disorders. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
dc.description.sponsorshipLipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - ANR-11-LABX-0021en_US
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enEndocannabinoid system
dc.subject.enCB1R antagonist
dc.subject.enRimonabant
dc.subject.enSWISSADME prediction
dc.subject.enDrug discovery
dc.subject.enPharmacokinetics
dc.subject.enObesity
dc.title.enChemical Synthesis, Pharmacokinetic Properties and Biological Effects of JM-00266, a Putative Non-Brain Penetrant Cannabinoid Receptor 1 Inverse Agonist
dc.typeArticle de revueen_US
dc.identifier.doi10.3390/ijms23062923en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed35328343en_US
bordeaux.journalInternational journal of molecular sciencesen_US
bordeaux.volume23en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.issue6en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDSociété Francophone du Diabèteen_US
hal.exportfalse
dc.rights.ccCC BYen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.date=2022-03-08&rft.volume=23&rft.issue=6&rft.eissn=1661-6596&rft.issn=1661-6596&rft.au=MULLER,%20Tania&DEMIZIEUX,%20Laurent&TROY%20FIORAMONTI,%20Stephanie&BUCH,%20Chloe&LEEMPUT,%20Julia&rft.genre=article


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