G protein-coupled receptors are seven-transmembrane proteins that can be activated by free fatty acid. GW950 is a small-molecule agonist of GPR40 and GPR120 with pEC50 values of 7.32±0.03 and 5.46±0.09, respectively. It also induced intracellular Ca2+ mobilization in HEK293 cells expressing GPR40 (pEC50=7.32±0.03) or GPR120 (pEC50=5.46±0.09). In MIN6 mouse insulinoma cell line, GW9508 induced a concentration-dependent increase in high glucose (25mM)-stimulated insulin secretion with a pEC50 of 6.14±0.03[3]. The administration of 200mM GW9508 to the ear 1h before each DNFB treatment significantly attenuated ear swelling in BALB/c mice compared with the controls. GW9508 treatment also significantly reduced the expression of CCL5 and eosinophils infiltrating in the skin compared to the vehicle-treated group. In C57BL/6 mice subjected to DNFB-induced CHS, application of GW9508 at 10-100μM suppressed ear swelling in a dose-dependent manner[4].
GW9508 细胞实验
Cell Line
Concentration
Treated Time
Description
References
661W cells
14 µM
8 h
To study the effect of GW9508 on Hif1a protein expression
Nat Med. 2016 Apr;22(4):439-45.
661W cells
14 µM
12 h
To study the effect of GW9508 on Vegfa secretion
Nat Med. 2016 Apr;22(4):439-45.
CLU189 cells
100 μM
1 h
To evaluate the effect of GW9508 on IKK activity in CLU189 cells, results showed a trend but no significant reduction in IKK activity.
J Neuroinflammation. 2017 Apr 26;14(1):91.
BV2 cells
100 μM
1 h
To evaluate the effect of GW9508 on IKK activity in BV2 cells, results showed a significant trend in reducing IKK activity.
J Neuroinflammation. 2017 Apr 26;14(1):91.
Human neutrophils
1 and 10 μM
10 min
GW9508 increased neutrophil chemotaxis in response to IL-8 and enhanced neutrophil phagocytosis of E. coli.
GW9508 increased superoxide and H2O2 content at 5.6 mM and 8.3 mM glucose concentrations, but not at 16.7 mM glucose concentration.
Redox Rep. 2020 Dec;25(1):41-50.
roGFP2-Orp1 BRIN-BD11 cells
20 μM
60 min
GW9508 increased H2O2 content at 5.6 mM and 8.3 mM glucose concentrations, but not at 16.7 mM glucose concentration.
Redox Rep. 2020 Dec;25(1):41-50.
brown preadipocytes
100 μM
24 h
GW9508 treatment significantly induced the expression of UCP1, Glut1, and FGF21, and strongly increased the secretion of FGF21 protein.
Nat Commun. 2016 Nov 17;7:13479.
brown adipocytes
100 μM
24 h
GW9508 treatment significantly increased the thermogenic activity of brown adipocytes and promoted the release of FGF21.
Nat Commun. 2016 Nov 17;7:13479.
beige preadipocytes
100 μM
24 h
GW9508 treatment significantly induced the differentiation of beige adipocytes and promoted the release of FGF21.
Nat Commun. 2016 Nov 17;7:13479.
GW9508 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Vldlr−/− mice
Intraperitoneal
14 µM
Once daily for 7 days
To study the effect of GW9508 on retinal glucose uptake and RAP-like lesions
Nat Med. 2016 Apr;22(4):439-45.
Swiss mice
High-fat diet-induced obesity model
Intracerebroventricular injection
1.0 mM
Twice daily for 6 days
To evaluate the effect of GW9508 on energy efficiency and inflammatory gene expression in obese mice, results showed that GW9508 reduced energy efficiency and decreased the expression of inflammatory genes.
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