GW9508

• CAT Number: I005314
• CAS Number: 885101-89-3
• Molecular Formula: C22H21NO3
• Molecular Weight: 347.4
• Purity: ≥95%
• Target: Free Fatty Acid Receptors
• Solubility: DMSO 69 mg/ml; Water <1 mg/ml
• Storage: 3 years -20C powder
• IC50: 7.32 (pEC50) [1]
• InChIKey: DGENZVKCTGIDRZ-UHFFFAOYSA-N

GW9508 is a potent and selective agonist for FFA1 (GPR40) with pEC50 of 7.32, 100-fold selective against GPR120, stimulates insulin secretion in a glucose-sensitive manner.IC50 value: 7.32 (pEC50) [1]Target: GPR40GW9508 is shown to be at least 100-fold selective against 220 other GPCRs, 60 kinases, 63 proteases, seven integrins and 20 nuclear receptors including PPARα, δ and γ (pEC50 4.0, 4 and 4.9, respectively). GW9508 produces a concentration-dependent increase in intracellular Ca2+ concentrations via GPR40 receptor activation and the GPR120 receptor. GW9508 is active as an agonist at both GPR40 and GPR120, it is approximately 100-fold selective for GPR40 with respect to GPR120. GW9508 produces a concentration-dependent increase (pEC50=6.14) in glucose-stimulated insulin secretion at high glucose levels (25 mM). GW9508 dose dependently stimulated insulin secretion in a glucose-sensitive manner in MIN6 cells. Furthermore, GW9508 is able to potentiate the KCl-mediated increase in insulin secretion in MIN6 cells. [1] GW9508 induced hyperpolarization and opening of KATP channels in rat β-cells. [2] GW9508 inhibits CCL17 and CCL5 expression in a pertussis toxin-sensitive manner. GW9508 further suppresses expression of IL-11, IL-24, and IL-33 induced in HaCaT cells by TNF-α and IFN-γ. GW9508 also inhibits CCL5 and CXCL10 production by normal human epidermal keratinocytes. [3]

Reference

1:GW9508, a free fatty acid receptor agonist, specifically induces cell death in bone resorbing precursor cells through increased oxidative stress from mitochondrial origin. Philippe C, Wauquier F, Léotoing L, Coxam V, Wittrant Y.Exp Cell Res. 2013 Nov 15;319(19):3035-41. doi: 10.1016/j.yexcr.2013.08.013. Epub 2013 Aug 22. PMID: 23973666 2:GW9508 inhibits insulin secretion by activating ATP-sensitive potassium channels in rat pancreatic β-cells. Zhao YF, Wang L, Zha D, Qiao L, Lu L, Yu J, Qu P, Sun Q, Qiu J, Chen C.J Mol Endocrinol. 2013 Jun 1;51(1):69-77. doi: 10.1530/JME-13-0019. Print 2013. PMID: 23628491 3:A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. Fujita T, Matsuoka T, Honda T, Kabashima K, Hirata T, Narumiya S.J Invest Dermatol. 2011 Aug;131(8):1660-7. doi: 10.1038/jid.2011.123. Epub 2011 May 19. PMID: 21593768 Free Article4:Insight into analysis of interactions of GW9508 to wild-type and H86F and H137F GPR40: a combined QM/MM study and pharmacophore modeling. Lu SY, Jiang YJ, Zou JW, Luo HB, Wu TX.J Mol Graph Model. 2011 Apr;29(6):818-25. doi: 10.1016/j.jmgm.2011.01.006. Epub 2011 Feb 1. PMID: 21334233