GW9508

製品コードS8014 バッチS801401

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H21NO3
分子量 347.41 CAS No. 885101-89-3
Solubility (25°C)* 体外 DMSO 69 mg/mL (198.61 mM)
Ethanol 69 mg/mL (198.61 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
2%DMSO 40%PEG300 2%Tween80 56%ddH2O
2.0mg/ml Taking the 1 mL working solution as an example, add 20 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 560 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]
特徴 The effects of GW9508 on insulin secretion are reversed by GW1100, while linoleic acid-stimulated insulin secretion is partially attenuated by GW1100.

プロトコル(参考用のみ)

キナーゼアッセイ 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.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Strained contacts with the cell membrane may influence ligand affinity to G protein coupled receptors: a case of free fatty acid receptor 1 agonists [ J Enzyme Inhib Med Chem, 2021, 36(1):1651-1658] PubMed: 34294008
Exploring Bulky Natural and Natural-Like Periphery in the Design of P-(Benzyloxy)phenylpropionic Acid Agonists of Free Fatty Acid Receptor 1 (GPR40) [ Bioorg Chem, 2020, 99:103830] PubMed: 32289588
Exploration of the nitrogen heterocyclic periphery around the core of the advanced FFA1 agonist fasiglifam (TAK-875) [ Arch Pharm (Weinheim), 2020, e2000275] PubMed: 33270252
Pharmacokinetics and metabolism of GW9508 in rat by liquid chromatography/electrospray ionization tandem mass spectrometry. [ J Pharm Biomed Anal, 2019, 170:176-186] PubMed: 30927663
AMPK/GSK3β/β-catenin cascade-triggered overexpression of CEMIP promotes migration and invasion in anoikis-resistant prostate cancer cells by enhancing metabolic reprogramming [Zhang P FASEB J, 2018, 32(7):3924-3935] PubMed: 29505302
GPR40 modulates epileptic seizure and NMDA receptor function. [ Sci Adv, 2018, 4(10):eaau2357] PubMed: 30345361
Polar aromatic periphery increases agonist potency of spirocyclic free fatty acid receptor (GPR40) agonists inspired by LY2881835. [ Eur J Med Chem, 2017, 127:357-368] PubMed: 28076825
Continued SAR exploration of 1,2,4-thiadiazole-containing scaffolds in the design of free fatty acid receptor 1 (GPR40) agonists [ Eur J Med Chem, 2017, 140:229-238] PubMed: 28938138
Novel FFA1 (GPR40) agonists containing spirocyclic periphery: polar azine periphery as a driver of potency [Krasavin M J Enzyme Inhib Med Chem, 2017, 32(1):29-36] PubMed: 27781494
Purinergic P2X7 receptor mediates acetaldehyde-induced hepatic stellate cells activation via PKC-dependent GSK3β pathway [Wu X Int Immunopharmacol, 2017, 43:164-171] PubMed: 28061416

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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