GW9508

{{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | IUPAC_name = 3-[4-[(3-phenoxyphenyl)methylamino]phenyl]propanoic acid | image = GW9508_structure.png | image_class = skin-invert-image | width =

| tradename = | routes_of_administration =

| C=22 | H=21 | N=1 | O=3 | smiles = C1=CC=C(C=C1)OC2=CC=CC(=C2)CNC3=CC=C(C=C3)CCC(=O)O | StdInChI = 1S/C22H21NO3/c24-22(25)14-11-17-9-12-19(13-10-17)23-16-18-5-4-8-21(15-18)26-20-6-2-1-3-7-20/h1-10,12-13,15,23H,11,14,16H2,(H,24,25) | StdInChIKey = DGENZVKCTGIDRZ-UHFFFAOYSA-N }}

'''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,<ref>{{cite journal | vauthors = Briscoe CP, Peat AJ, McKeown SC, Corbett DF, Goetz AS, Littleton TR, McCoy DC, Kenakin TP, Andrews JL, Ammala C, Fornwald JA, Ignar DM, Jenkinson S | title = Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: Identification of agonist and antagonist small molecules | journal = British Journal of Pharmacology | volume = 148 | issue = 5 | pages = 619–628 | date = 2006 | pmid = 16702987 | pmc = 1751878 | doi = 10.1038/sj.bjp.0706770 }}</ref> 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,<ref>{{cite journal | vauthors = Hudson BD, Shimpukade B, Milligan G, Ulven T | title = The Molecular Basis of Ligand Interaction at Free Fatty Acid Receptor 4 (FFA4/GPR120) | journal = The Journal of Biological Chemistry | volume = 289 | issue = 29 | pages = 20345–20358 | date = 2014 | pmid = 24860101 | pmc = 4106347 | doi = 10.1074/jbc.M114.561449 | doi-access = free }}</ref> due to a historical lack of availability of highly selective FFAR4 agonists.<ref>{{cite journal | vauthors = Moniri NH | title = Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders | journal = Biochemical Pharmacology | volume = 110-111 | pages = 1–15 | date = 2016 | pmid = 26827942 | pmc = 6415295 | doi = 10.1016/j.bcp.2016.01.021 }}</ref> It has antiinflammatory effects<ref>{{cite journal | vauthors = Fujita T, Matsuoka T, Honda T, Kabashima K, Hirata T, Narumiya S | title = A GPR40 Agonist GW9508 Suppresses CCL5, CCL17, and CXCL10 Induction in Keratinocytes and Attenuates Cutaneous Immune Inflammation | journal = The Journal of Investigative Dermatology | volume = 131 | issue = 8 | pages = 1660–1667 | date = 2011 | pmid = 21593768 | doi = 10.1038/jid.2011.123 }}</ref><ref>{{cite journal | vauthors = Souza PR, Walker ME, Goulding NJ, Dalli J, Perretti M, Norling LV | title = The GPR40 Agonist GW9508 Enhances Neutrophil Function to Aid Bacterial Clearance During E. Coli Infections | journal = Frontiers in Immunology | volume = 11 | article-number = 573019 | date = 2020 | pmid = 33133087 | pmc = 7550532 | doi = 10.3389/fimmu.2020.573019 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Zou Y, Zhang B, Jiang K, Zhou X, Tang Q, Chen S, Wu Q, Zhao X, Zhang X | title = GPR40 inhibits microglia-mediated neuroinflammation via the NLRP3/IL-1β/Glutaminase pathway after subarachnoid hemorrhage | journal = Biochemical Pharmacology | volume = 238 | article-number = 116971 | date = 2025 | pmid = 40318813 | doi = 10.1016/j.bcp.2025.116971 | doi-access = free }}</ref> and has also been used to study the role of FFAR1 and FFAR4 in various processes such as regulation of insulin<ref>{{cite journal | vauthors = Hashimoto T, Mogami H, Tsuriya D, Morita H, Sasaki S, Kumada T, Suzuki Y, Urano T, Oki Y, Suda T | title = G-protein-coupled receptor 40 agonist GW9508 potentiates glucose-stimulated insulin secretion through activation of protein kinase Cα and ε in INS-1 cells | journal = PLOS ONE | volume = 14 | issue = 9 | article-number = e0222179 | date = 2019 | pmid = 31498851 | pmc = 6733457 | doi = 10.1371/journal.pone.0222179 | doi-access = free }}</ref> and ghrelin<ref>{{cite journal | vauthors = Gong Z, Yoshimura M, Aizawa S, Kurotani R, Zigman JM, Sakai T, Sakata I | title = G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 306 | issue = 1 | pages = E28–E35 | date = 2014 | pmid = 24222669 | doi = 10.1152/ajpendo.00306.2013 }}</ref> release, immune system function,<ref>{{cite journal | vauthors = Dragano NR, Solon C, Ramalho AF, De Moura RF, Razolli DS, Christiansen E, Azevedo C, Ulven T, Velloso LA | title = Polyunsaturated fatty acid receptors, GPR40 and GPR120, are expressed in the hypothalamus and control energy homeostasis and inflammation | journal = Journal of Neuroinflammation | volume = 14 | issue = 1 | article-number = 91 | date = 2017 | pmid = 28446241 | pmc = 5405534 | doi = 10.1186/s12974-017-0869-7 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Li Y, Yu H, Lopes-Virella MF, Huang Y | title = GPR40/GPR120 Agonist GW9508 Improves Metabolic Syndrome-Exacerbated Periodontitis in Mice | journal = International Journal of Molecular Sciences | volume = 25 | issue = 17 | page = 9622 | date = 2024 | pmid = 39273569 | pmc = 11394899 | doi = 10.3390/ijms25179622 | doi-access = free }}</ref> and maintenance of bone density.<ref>{{cite journal | vauthors = Wauquier F, Philippe C, Léotoing L, Mercier S, Davicco MJ, Lebecque P, Guicheux J, Pilet P, Miot-Noirault E, Poitout V, Alquier T, Coxam V, Wittrant Y | title = The Free Fatty Acid Receptor G Protein-coupled Receptor 40 (GPR40) Protects from Bone Loss through Inhibition of Osteoclast Differentiation | journal = The Journal of Biological Chemistry | volume = 288 | issue = 9 | pages = 6542–6551 | date = 2013 | pmid = 23335512 | pmc = 3585087 | doi = 10.1074/jbc.M112.429084 | doi-access = free }}</ref>

== References == {{Reflist}}

==Further reading== {{refbegin}} * {{cite journal | vauthors = Nishinaka T, Yamashita T, Nakamoto K, Kasuya F, Tokuyama S | title = Involvement of the Long-Chain Fatty Acid Receptor GPR40 in Depression-Related Behavior | journal = Journal of Pharmacological Sciences | volume = 125 | issue = 1 | pages = 112–115 | date = 2014 | pmid = 24758921 | doi = 10.1254/jphs.14001sc }} * {{cite journal | vauthors = Tsukahara T, Watanabe K, Watanabe T, Yamagami H, Sogawa M, Tanigawa T, Shiba M, Tominaga K, Fujiwara Y, Maeda K, Hirakawa K, Arakawa T | title = Tumor Necrosis Factor α Decreases Glucagon-Like Peptide-2 Expression by Up-Regulating G-Protein–Coupled Receptor 120 in Crohn Disease | journal = The American Journal of Pathology | volume = 185 | issue = 1 | pages = 185–196 | date = 2015 | pmid = 25447053 | doi = 10.1016/j.ajpath.2014.09.010 | doi-access = free }} * {{cite journal | vauthors = Liu Z, Hopkins MM, Zhang Z, Quisenberry CB, Fix LC, Galvan BM, Meier KE | title = Omega-3 Fatty Acids and Other FFA4 Agonists Inhibit Growth Factor Signaling in Human Prostate Cancer Cells | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 352 | issue = 2 | pages = 380–394 | date = 2015 | pmid = 25491146 | pmc = 4293432 | doi = 10.1124/jpet.114.218974 }} * {{cite journal | vauthors = Quesada-López T, Cereijo R, Turatsinze JV, Planavila A, Cairó M, Gavaldà-Navarro A, Peyrou M, Moure R, Iglesias R, Giralt M, Eizirik DL, Villarroya F | title = The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes | journal = Nature Communications | volume = 7 | article-number = 13479 | date = 2016 | pmid = 27853148 | pmc = 5118546 | doi = 10.1038/ncomms13479 | bibcode = 2016NatCo...713479Q }} * {{cite journal | vauthors = An T, Zhang X, Li H, Dou L, Huang X, Man Y, Zhang X, Shen T, Li G, Li J, Tang W | title = GPR120 facilitates cholesterol efflux in macrophages through activation of AMPK signaling pathway | journal = The FEBS Journal | volume = 287 | issue = 23 | pages = 5080–5095 | date = 2020 | pmid = 32243091 | doi = 10.1111/febs.15310 }} * {{cite journal | vauthors = Xiao J, Cai T, Fang Y, Liu R, Flores JJ, Wang W, Gao L, Liu Y, Lu Q, Tang L, Zhang JH, Lu H, Tang J | title = Activation of GPR40 attenuates neuroinflammation and improves neurological function via PAK4/CREB/KDM6B pathway in an experimental GMH rat model | journal = Journal of Neuroinflammation | volume = 18 | issue = 1 | article-number = 160 | date = 2021 | pmid = 34275493 | pmc = 8286626 | doi = 10.1186/s12974-021-02209-9 | doi-access = free }} * {{cite journal | vauthors = Sadamura Y, Thapa S, Mizunuma R, Kambe Y, Hirasawa A, Nakamoto K, Tokuyama S, Yoshimoto K, Arita K, Miyata A, Oyoshi T, Kurihara T | title = FFAR1/GPR40 Contributes to the Regulation of Striatal Monoamine Releases and Facilitation of Cocaine-Induced Locomotor Activity in Mice | journal = Frontiers in Pharmacology | volume = 12 | article-number = 699026 | date = 2021 | pmid = 34489696 | pmc = 8417570 | doi = 10.3389/fphar.2021.699026 | doi-access = free }} {{refend}}

Category:Experimental drugs Category:Anilines Category:Propionic acids Category:Diphenyl ethers