Chemistry:GLPG0974
From HandWiki
GLPG0974 is an experimental drug which acts as a reasonably potent and selective antagonist for the free fatty acid receptor FFAR2 (GPR43). It was originally developed as a potential medication for ulcerative colitis, and while it was not developed as a medicine for this application it has remained widely used as a pharmacological tool compound for research into the FFAR2 receptor, as one of the relatively few selective FFAR2 antagonists available.[1][2][3][4][5] Despite its antagonist action, it can also act as a positive allosteric modulator of FFAR2 under some conditions, which can complicate interpretation of results obtained using GLPG0974 in the presence of other FFAR2 ligands.[6]
References
- ↑ "Discovery and optimization of an azetidine chemical series as a free fatty acid receptor 2 (FFA2) antagonist: from hit to clinic". Journal of Medicinal Chemistry 57 (23): 10044–10057. December 2014. doi:10.1021/jm5012885. PMID 25380412.
- ↑ "Safety, pharmacokinetics and pharmacodynamics of GLPG0974, a potent and selective FFA2 antagonist, in healthy male subjects". British Journal of Clinical Pharmacology 82 (1): 139–148. July 2016. doi:10.1111/bcp.12900. PMID 26852904.
- ↑ "FFA2 activation combined with ulcerogenic COX inhibition induces duodenal mucosal injury via the 5-HT pathway in rats". American Journal of Physiology. Gastrointestinal and Liver Physiology 313 (2): G117–G128. August 2017. doi:10.1152/ajpgi.00041.2017. PMID 28526687.
- ↑ "Constitutively active GPR43 is crucial for proper leukocyte differentiation". FASEB Journal 37 (1): e22676. January 2023. doi:10.1096/fj.202201591R. PMID 36468834.
- ↑ "Structural insights into lipid chain-length selectivity and allosteric regulation of FFA2". Nature Communications 16 (1). March 2025. doi:10.1038/s41467-025-57983-4. PMID 40140663. Bibcode: 2025NatCo..16.2809K.
- ↑ "Allosteric receptor modulation uncovers an FFA2R antagonist as a positive orthosteric modulator/agonist in disguise". Cellular Signalling 90. February 2022. doi:10.1016/j.cellsig.2021.110208. PMID 34856356.
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