GW9508

Catalog No.S8014

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.

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GW9508 Chemical Structure

GW9508 Chemical Structure
Molecular Weight: 347.41

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Quality Control & MSDS

Product Information

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Product Description

Biological Activity

Description 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.
Targets GPR40 [1] GPR120 [1]
IC50 7.32(pEC50) 5.46(pEC50)
In vitro GW9508 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]
In vivo
Features The effects of GW9508 on insulin secretion are reversed by GW1100, while linoleic acid-stimulated insulin secretion is partially attenuated by GW1100.

Protocol(Only for Reference)

Kinase Assay: [1]

Measurement of intracellular Ca2+ release HEK-293 cells, stably transfected to express the human macrophage scavenging receptor are maintained in Dulbecco's modified Eagles medium (DMEM; high glucose) containing 10% (v/v) heat-inactivated fetal calf serum. The expression of this receptor by the HEK-293 cells enhances their ability to stick to tissue culture treated plasticware. Cells are harvested using an enzyme-free cell dissociation buffer. Of this solution, 5 ml, is added and allowed to wash over the cells for 30 s. The solution is then removed and the cells return to the incubator for 5 min. Following a gently tapping of the flask the cells are resuspended in media. For GPR40 studies cells are transduced with GPR40 BacMam baculovirus at a multiplicity of infection (MOI) of 25. Control cells are not transduced with virus. The cells are plated at a concentration of 10,000 cells per well in black 384-well clear bottom tissue culture treated plates. The cells are cultured for 24 h at 37°C in a humidified 5% CO2 air environment to allow for protein expression. Subsequently, the medium is removed from the wells and replaced with 40 μl of Calcium-3 dye. The cells are allowed to load with dye for 1 h at 37°C in a cell culture incubator. The plates are then allowed to cool to room temperature for 20 min. All compounds are diluted to appropriate concentrations in Calcium-3 dye. Compounds are added during the assay by the FLIPR3 instrument in 10 μL per well volumes and the wells are read by the instrument every 2 s for 90 s. Antagonist studies are performed in a similar format. Antagonist is added to the well in a 10 μL volume and the plates are incubated at room temperature for 15 min before the second addition of 10 μL per well of an ED80 concentration of agonist.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Briscoe CP, et al. Br J Pharmacol, 2006, 148(5), 619-628.

[2] Zhao YF, et al. J Endocrinol, 2008, 198(3), 533-540.

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Chemical Information

Molecular Weight (MW) 347.41
Formula

 

C22H21NO3
CAS No. 885101-89-3
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 69 mg/mL (198.61 mM)
Ethanol 69 mg/mL (198.61 mM)
Water <1 mg/mL (<1 mM)
In vivo
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name Benzenepropanoic acid, 4-[[(3-phenoxyphenyl)methyl]amino]-

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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