{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:08:26Z","timestamp":1789348106693,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007900","name":"University of Central Florida","doi-asserted-by":"publisher","award":["UCFstartup"],"award-info":[{"award-number":["UCFstartup"]}],"id":[{"id":"10.13039\/100007900","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007900","name":"University of Central Florida","doi-asserted-by":"publisher","award":["COMseedfunding"],"award-info":[{"award-number":["COMseedfunding"]}],"id":[{"id":"10.13039\/100007900","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R01HL166820\u201001"],"award-info":[{"award-number":["NIH R01HL166820\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 DC021103"],"award-info":[{"award-number":["R21 DC021103"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,9,14]]},"abstract":"<jats:p>\n                    GPR84, a medium\u2010chain fatty acid (MCFA)\u2010sensing G protein\u2010coupled receptor, plays a significant role in immune regulation. Despite its therapeutic potential, structurally diverse and well\u2010characterized chemical probes of GPR84 remain limited. In the current study, we developed a novel structure\u2010guided and dual\u2010route pipeline to explore and prioritize small\u2010molecule scaffolds compatible with the GPR84 orthosteric pocket, with pharmacophore\u2010based ZINC screening and LigBuilder\u2010based de novo design, accompanied by molecular docking, ADME filtering, and molecular dynamics, followed by immunoregulatory activity validation. ZINC screening identified ZINC149375 (SC787) and ZINC76994316 (Z109), which were further evaluated by 500\u2010ns molecular dynamics simulations. Additionally, LIG081 and LIG133 from the LigBuilder\u2010derived series emerged as computationally prioritized de novo candidates with favorable and persistent predicted interactions within the GPR84 orthosteric pocket. These ZINC\u2010derived compounds demonstrated potent immune cell\u2010dependent immunomodulatory activities associated with GPR84 functional agonism. SC787 and Z109 promote proinflammatory signaling in macrophages while suppressing activation and effector cytokine production in activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Collectively, this study identifies structurally prioritized GPR84 pocket\u2010compatible scaffolds for future receptor\u2010focused immunological activity validation and medicinal chemistry optimization.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70488","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:09:37Z","timestamp":1788829777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure\u2010Guided Identification of GPR84 Ligand Candidates With Potential Immunomodulatory Activities"],"prefix":"10.1002","volume":"21","author":[{"given":"Ha\u2010Anh Thi","family":"Pham","sequence":"first","affiliation":[{"name":"Faculty of Biotechnology Hanoi University of Pharmacy  Hanoi 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