Chemistry:GW9508
From HandWiki
GW9508 is an experimental drug which acts as a mixed agonist for the free fatty acid receptors FFAR1 (GPR40) and FFAR4 (GPR120). It is around 60x more potent as an agonist at FFAR1,[1] but has nevertheless often been used as a model agonist for FFAR4 especially in tissues which lack FFAR1 or in the presence of FFAR1 antagonists,[2] due to a historical lack of availability of highly selective FFAR4 agonists.[3] It has antiinflammatory effects[4][5][6] and has also been used to study the role of FFAR1 and FFAR4 in various processes such as regulation of insulin[7] and ghrelin[8] release, immune system function,[9][10] and maintenance of bone density.[11]
References
- ↑ "Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: Identification of agonist and antagonist small molecules". British Journal of Pharmacology 148 (5): 619–628. 2006. doi:10.1038/sj.bjp.0706770. PMID 16702987.
- ↑ "The Molecular Basis of Ligand Interaction at Free Fatty Acid Receptor 4 (FFA4/GPR120)". The Journal of Biological Chemistry 289 (29): 20345–20358. 2014. doi:10.1074/jbc.M114.561449. PMID 24860101.
- ↑ "Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders". Biochemical Pharmacology 110-111: 1–15. 2016. doi:10.1016/j.bcp.2016.01.021. PMID 26827942.
- ↑ "A GPR40 Agonist GW9508 Suppresses CCL5, CCL17, and CXCL10 Induction in Keratinocytes and Attenuates Cutaneous Immune Inflammation". The Journal of Investigative Dermatology 131 (8): 1660–1667. 2011. doi:10.1038/jid.2011.123. PMID 21593768.
- ↑ "The GPR40 Agonist GW9508 Enhances Neutrophil Function to Aid Bacterial Clearance During E. Coli Infections". Frontiers in Immunology 11: 573019. 2020. doi:10.3389/fimmu.2020.573019. PMID 33133087.
- ↑ "GPR40 inhibits microglia-mediated neuroinflammation via the NLRP3/IL-1β/Glutaminase pathway after subarachnoid hemorrhage". Biochemical Pharmacology 238. 2025. doi:10.1016/j.bcp.2025.116971. PMID 40318813.
- ↑ "G-protein-coupled receptor 40 agonist GW9508 potentiates glucose-stimulated insulin secretion through activation of protein kinase Cα and ε in INS-1 cells". PLOS ONE 14 (9): e0222179. 2019. doi:10.1371/journal.pone.0222179. PMID 31498851.
- ↑ "G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro". American Journal of Physiology. Endocrinology and Metabolism 306 (1): E28–E35. 2014. doi:10.1152/ajpendo.00306.2013. PMID 24222669.
- ↑ "Polyunsaturated fatty acid receptors, GPR40 and GPR120, are expressed in the hypothalamus and control energy homeostasis and inflammation". Journal of Neuroinflammation 14 (1). 2017. doi:10.1186/s12974-017-0869-7. PMID 28446241.
- ↑ "GPR40/GPR120 Agonist GW9508 Improves Metabolic Syndrome-Exacerbated Periodontitis in Mice". International Journal of Molecular Sciences 25 (17): 9622. 2024. doi:10.3390/ijms25179622. PMID 39273569.
- ↑ "The Free Fatty Acid Receptor G Protein-coupled Receptor 40 (GPR40) Protects from Bone Loss through Inhibition of Osteoclast Differentiation". The Journal of Biological Chemistry 288 (9): 6542–6551. 2013. doi:10.1074/jbc.M112.429084. PMID 23335512.
Further reading
- "Involvement of the Long-Chain Fatty Acid Receptor GPR40 in Depression-Related Behavior". Journal of Pharmacological Sciences 125 (1): 112–115. 2014. doi:10.1254/jphs.14001sc. PMID 24758921.
- "Tumor Necrosis Factor α Decreases Glucagon-Like Peptide-2 Expression by Up-Regulating G-Protein–Coupled Receptor 120 in Crohn Disease". The American Journal of Pathology 185 (1): 185–196. 2015. doi:10.1016/j.ajpath.2014.09.010. PMID 25447053.
- "Omega-3 Fatty Acids and Other FFA4 Agonists Inhibit Growth Factor Signaling in Human Prostate Cancer Cells". The Journal of Pharmacology and Experimental Therapeutics 352 (2): 380–394. 2015. doi:10.1124/jpet.114.218974. PMID 25491146.
- "The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes". Nature Communications 7. 2016. doi:10.1038/ncomms13479. PMID 27853148. Bibcode: 2016NatCo...713479Q.
- "GPR120 facilitates cholesterol efflux in macrophages through activation of AMPK signaling pathway". The FEBS Journal 287 (23): 5080–5095. 2020. doi:10.1111/febs.15310. PMID 32243091.
- "Activation of GPR40 attenuates neuroinflammation and improves neurological function via PAK4/CREB/KDM6B pathway in an experimental GMH rat model". Journal of Neuroinflammation 18 (1). 2021. doi:10.1186/s12974-021-02209-9. PMID 34275493.
- "FFAR1/GPR40 Contributes to the Regulation of Striatal Monoamine Releases and Facilitation of Cocaine-Induced Locomotor Activity in Mice". Frontiers in Pharmacology 12: 699026. 2021. doi:10.3389/fphar.2021.699026. PMID 34489696.
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