Synonym
GW9508; GW-9508; GW 9508.
IUPAC/Chemical Name
3-(4-((3-phenoxybenzyl)amino)phenyl)propanoic acid
InChi Key
DGENZVKCTGIDRZ-UHFFFAOYSA-N
InChi Code
InChI=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)
SMILES Code
O=C(O)CCC1=CC=C(NCC2=CC=CC(OC3=CC=CC=C3)=C2)C=C1
Appearance
white to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
GW9508 is a potent and selective G protein-coupled receptors FFA1 (GPR40) and GPR120 agonist with pEC50s of 7.32 and 5.46, respectively.
In vitro activity:
The human aortic endothelial cells (HAECs) were treated with ox-LDL (100 μg/mL) in the presence or absence of GW9508 (50 μM) or AH9614 (1 μM) for 24 h. The protective effect of GW9508 on ox-LDL-induced endothelial toxicity indicates that the activation of the GPR120 receptor could have a beneficial role to counter ox-LDL. Tts influence on endothelial senescence was then determined by measuring SA-β-gal activity. Compared to nontreated cells, ox-LDL treatment for 7 days induced more than a 3-fold increase in SA-βgal activity, but the presence of the same dose of GW9508 inhibited more than half of SA-β-gal activity (Figure33). The normal growing HAEC population had about 51% G0/G1 phase cells at arrest, and while ox-LDL induced a 79% G1/G0 phase cell population, the presence of GW9508 significantly attenuated ox-LDL-induced cell cycle arrest, and roughly 62% population of the cells was at the G1/G0 phase arrest (Figure44). In the same 24 h ox-LDL experiment, GW9508 inhibited both p53 and PAI-1 ox-LDLinduced expressions at mRNA (Figure55A) and protein levels (Figure55B), respectively. Furthermore, it was found that GW9508 exhibited robust promotion of ox-LDL-induced nuclear translocation of NRF2 in the 24 h treatment experiment. These facts indicate the role of GW9508 in endothelial cells, which is solely dependent on GPR120 signals.
Reference: ACS Omega. 2020 Dec 22; 5(50): 32195–32202. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758881/
In vivo activity:
To examine effects of GW9508 on a Th2-type inflammation, repeated DNFB treatment was adopted in BALB/c mice. Repeated elicitation with hapten results in a shift from Th1-mediated to Th2-mediated inflammation (Kabashima et al., 2003; Inagaki et al., 2006), which mimics AD. From the fifth to the ninth elicitation, 20μl of 200μM GW9508 or vehicle were topically applied to the ear 1h before each DNFB application. Treatment with GW9508 resulted in significant reduction of ear swelling compared with the control mice (Figure 5a). Histological examination revealed diminished epidermal thickening and attenuated cell infiltration in the dermis of the GW9508-treated group compared with the vehicle-treated group (Figure 5b). Immunostaining for CCL5 revealed that the CCL5 signal was enriched in the cytoplasm of keratinocytes of the skin of the vehicle-treated animals, and that the GW9508 treatment markedly attenuated the signal (Figure 5d). Consistent with this suppression, the number of eosinophils infiltrating in the skin was significantly suppressed in the GW9508-treated group compared with the control, vehicle-treated group (Figure 5b and e). Attenuation of mast cell infiltration was also noted in the GW9508-treated group (Figure 5f). These data collectively suggest that GW9508 reduces CCL5 production in keratinocytes and infiltration of eosinophils and mast cells, and attenuates ear swelling in repeated DNFB treatment, a model of AD.
Reference: J Invest Dermatol. 2011 Aug;131(8):1660-7. https://pubmed.ncbi.nlm.nih.gov/21593768/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
30.0 |
86.35 |
| Ethanol |
30.0 |
86.35 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
347.41
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Liu R, Cheng F, Zeng K, Li W, Lan J. GPR120 Agonist GW9508 Ameliorated Cellular Senescence Induced by ox-LDL. ACS Omega. 2020 Dec 8;5(50):32195-32202. doi: 10.1021/acsomega.0c03581. PMID: 33376857; PMCID: PMC7758881. 2. Hashimoto T, Mogami H, Tsuriya D, Morita H, Sasaki S, Kumada T, Suzuki Y, Urano T, Oki Y, Suda T. 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. 2019 Sep 9;14(9):e0222179. doi: 10.1371/journal.pone.0222179. PMID: 31498851; PMCID: PMC6733457
3. Souza PR, Walker ME, Goulding NJ, Dalli J, Perretti M, Norling LV. The GPR40 Agonist GW9508 Enhances Neutrophil Function to Aid Bacterial Clearance During E. coli Infections. Front Immunol. 2020 Sep 29;11:573019. doi: 10.3389/fimmu.2020.573019. PMID: 33133087; PMCID: PMC7550532.
4. Fujita T, Matsuoka T, Honda T, Kabashima K, Hirata T, Narumiya S. A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. J Invest Dermatol. 2011 Aug;131(8):1660-7. doi: 10.1038/jid.2011.123. Epub 2011 May 19. PMID: 21593768
In vitro protocol:
1. Liu R, Cheng F, Zeng K, Li W, Lan J. GPR120 Agonist GW9508 Ameliorated Cellular Senescence Induced by ox-LDL. ACS Omega. 2020 Dec 8;5(50):32195-32202. doi: 10.1021/acsomega.0c03581. PMID: 33376857; PMCID: PMC7758881. 2. Hashimoto T, Mogami H, Tsuriya D, Morita H, Sasaki S, Kumada T, Suzuki Y, Urano T, Oki Y, Suda T. 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. 2019 Sep 9;14(9):e0222179. doi: 10.1371/journal.pone.0222179. PMID: 31498851; PMCID: PMC6733457
In vivo protocol:
1. Souza PR, Walker ME, Goulding NJ, Dalli J, Perretti M, Norling LV. The GPR40 Agonist GW9508 Enhances Neutrophil Function to Aid Bacterial Clearance During E. coli Infections. Front Immunol. 2020 Sep 29;11:573019. doi: 10.3389/fimmu.2020.573019. PMID: 33133087; PMCID: PMC7550532. 2. Fujita T, Matsuoka T, Honda T, Kabashima K, Hirata T, Narumiya S. A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. J Invest Dermatol. 2011 Aug;131(8):1660-7. doi: 10.1038/jid.2011.123. Epub 2011 May 19. PMID: 21593768.
1: Philippe C, Wauquier F, Léotoing L, Coxam V, Wittrant Y. GW9508, a free fatty acid receptor agonist, specifically induces cell death in bone resorbing precursor cells through increased oxidative stress from mitochondrial origin. Exp Cell Res. 2013 Nov 15;319(19):3035-41. doi: 10.1016/j.yexcr.2013.08.013. Epub 2013 Aug 22. PubMed PMID: 23973666.
2: Zhao YF, Wang L, Zha D, Qiao L, Lu L, Yu J, Qu P, Sun Q, Qiu J, Chen C. GW9508 inhibits insulin secretion by activating ATP-sensitive potassium channels in rat pancreatic β-cells. J Mol Endocrinol. 2013 Jun 1;51(1):69-77. doi: 10.1530/JME-13-0019. Print 2013. PubMed PMID: 23628491.
3: Fujita T, Matsuoka T, Honda T, Kabashima K, Hirata T, Narumiya S. A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. J Invest Dermatol. 2011 Aug;131(8):1660-7. doi: 10.1038/jid.2011.123. Epub 2011 May 19. PubMed PMID: 21593768.
4: Lu SY, Jiang YJ, Zou JW, Luo HB, Wu TX. Insight into analysis of interactions of GW9508 to wild-type and H86F and H137F GPR40: a combined QM/MM study and pharmacophore modeling. J Mol Graph Model. 2011 Apr;29(6):818-25. doi: 10.1016/j.jmgm.2011.01.006. Epub 2011 Feb 1. PubMed PMID: 21334233.
