{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T05:39:04Z","timestamp":1793597944456,"version":"4.5.0"},"reference-count":17,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["NCT05694741"],"award-info":[{"award-number":["NCT05694741"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.jpet.2025.103683","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T02:17:59Z","timestamp":1756433879000},"page":"103683","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Preclinical evaluation and first-in-human phase 1 trial of AZD0186, a novel, oral small molecule glucagon-like peptide-1 receptor agonist"],"prefix":"10.1016","volume":"392","author":[{"given":"Weier","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1400-3398","authenticated-orcid":false,"given":"Simina M.","family":"Boca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2193-9415","authenticated-orcid":false,"given":"Alessandro","family":"Boianelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Fredberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lundqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joss","family":"Field","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl A.","family":"Brighton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2829-3098","authenticated-orcid":false,"given":"Arjan","family":"Snijder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernilla","family":"Grundevik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Eckern\u00e4s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika Maria","family":"Tr\u00e4ff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Polla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7349-887X","authenticated-orcid":false,"given":"Daniel","family":"Pettersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-0958","authenticated-orcid":false,"given":"Sami","family":"Omar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4134-3849","authenticated-orcid":false,"given":"David","family":"Janz\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Melin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"van Zuydam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Logue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Wallenius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.jpet.2025.103683_bib1","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.cmet.2018.03.001","article-title":"Mechanisms of action and therapeutic application of glucagon-like peptide-1","volume":"27","author":"Drucker","year":"2018","journal-title":"Cell Metab"},{"key":"10.1016\/j.jpet.2025.103683_bib2","author":"Lobstein"},{"issue":"11","key":"10.1016\/j.jpet.2025.103683_bib3","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.2337\/dci22-0034","article-title":"Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"45","author":"Davies","year":"2022","journal-title":"Diabetes Care"},{"issue":"6","key":"10.1016\/j.jpet.2025.103683_bib4","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","article-title":"Biology of incretins: GLP-1 and GIP","volume":"132","author":"Baggio","year":"2007","journal-title":"Gastroenterology"},{"issue":"12","key":"10.1016\/j.jpet.2025.103683_bib5","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.2337\/db14-0849","article-title":"GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans","volume":"63","author":"van Bloemendaal","year":"2014","journal-title":"Diabetes"},{"key":"10.1016\/j.jpet.2025.103683_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2020.101102","article-title":"GLP-1 receptor agonists in the treatment of type 2 diabetes: state-of-the-art","volume":"46","author":"Nauck","year":"2021","journal-title":"Mol Metab"},{"key":"10.1016\/j.jpet.2025.103683_bib7","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.metabol.2019.04.014","article-title":"The incretin system in healthy humans: the role of GIP and GLP-1","volume":"96","author":"Holst","year":"2019","journal-title":"Metabolism"},{"key":"10.1016\/j.jpet.2025.103683_bib8","doi-asserted-by":"crossref","DOI":"10.1177\/2042018821997320","article-title":"GLP-1 receptor agonists: an updated review of head-to-head clinical studies","volume":"12","author":"Trujillo","year":"2021","journal-title":"Ther Adv Endocrinol Metab"},{"issue":"10","key":"10.1016\/j.jpet.2025.103683_bib9","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1111\/dom.15168","article-title":"Tolerability, safety and pharmacodynamics of oral, small-molecule glucagon-like peptide-1 receptor agonist danuglipron for type 2 diabetes: a 12-week, randomized, placebo-controlled, phase 2 study comparing different dose-escalation schemes","volume":"25","author":"Saxena","year":"2023","journal-title":"Diabetes Obes Metab"},{"issue":"10","key":"10.1016\/j.jpet.2025.103683_bib10","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1056\/NEJMoa2302392","article-title":"Daily oral GLP-1 receptor agonist orforglipron for adults with obesity","volume":"389","author":"Wharton","year":"2023","journal-title":"N Engl J Med"},{"issue":"2","key":"10.1016\/j.jpet.2025.103683_bib11","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/dom.16047","article-title":"Non-clinical and first-in-human characterization of ECC5004\/AZD5004, a novel once-daily, oral small-molecule GLP-1 receptor agonist","volume":"27","author":"Haggag","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"10.1016\/j.jpet.2025.103683_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2023.101772","article-title":"EndoC-betaH5 cells are storable and ready-to-use human pancreatic beta cells with physiological insulin secretion","volume":"76","author":"Blanchi","year":"2023","journal-title":"Mol Metab"},{"issue":"12","key":"10.1016\/j.jpet.2025.103683_bib13","doi-asserted-by":"crossref","first-page":"8208","DOI":"10.1021\/acs.jmedchem.1c01856","article-title":"A small-molecule oral agonist of the human glucagon-like peptide-1 receptor","volume":"65","author":"Griffith","year":"2022","journal-title":"J Med Chem"},{"issue":"20","key":"10.1016\/j.jpet.2025.103683_bib14","doi-asserted-by":"crossref","first-page":"11831","DOI":"10.1021\/acs.jmedchem.0c01033","article-title":"Predicting the human hepatic clearance of acidic and zwitterionic drugs","volume":"63","author":"Tess","year":"2020","journal-title":"J Med Chem"},{"issue":"10","key":"10.1016\/j.jpet.2025.103683_bib15","doi-asserted-by":"crossref","first-page":"R885","DOI":"10.1152\/ajpregu.00520.2015","article-title":"GLP-1 and weight loss: unraveling the diverse neural circuitry","volume":"310","author":"Kanoski","year":"2016","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"17","key":"10.1016\/j.jpet.2025.103683_bib16","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.140532","article-title":"Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist","volume":"5","author":"Willard","year":"2020","journal-title":"JCI Insight"},{"issue":"778","key":"10.1016\/j.jpet.2025.103683_bib17","doi-asserted-by":"crossref","first-page":"eadp5765","DOI":"10.1126\/scitranslmed.adp5765","article-title":"The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron","volume":"16","author":"Sloop","year":"2024","journal-title":"Sci Transl Med"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356525398964?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356525398964?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:58:05Z","timestamp":1761850685000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356525398964"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":17,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["S0022356525398964"],"URL":"https:\/\/doi.org\/10.1016\/j.jpet.2025.103683","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Preclinical evaluation and first-in-human phase 1 trial of AZD0186, a novel, oral small molecule glucagon-like peptide-1 receptor agonist","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jpet.2025.103683","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc. on behalf of American Society for Pharmacology and Experimental Therapeutics.","name":"copyright","label":"Copyright"}],"article-number":"103683"}}