| Size | Price | Stock | Qty |
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| 25mg |
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Purity: ≥98%
GW9508 (GW-9508) is a novel, potent and selective agonist for FFA1 (fatty acid receptor GPR40) with pEC50 of 7.32, and is 100-fold selective against GPR120, it stimulates insulin secretion in a glucose-sensitive manner. GW9508 is a GPR40/120 agonist and is different from the reported GPR40/120 agonist GW1100. When tested with HEK-293 (human embryonic kidney) cells expressing GPR40 or GRP120, GW9508 treatment increased intracellular Ca2+ concentration via activating GPR40/120 in a dose-dependent manner.
| Targets |
G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1); GW9508 activated human GPR40 with an EC50 of 1.2 μM in CHO cells stably expressing human GPR40, and 0.8 μM in mouse MIN6 pancreatic β-cells [1]
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| ln Vitro |
In HEK-293 cells expressing GPR40 (pEC50 of 7.32) or GPR120 (pEC50 of 5.46), GW9508 increases intracellular Ca2+ mobilization, but not in the parent HEK-293 cell line [1]. GW9508 concentration-dependently enhances glucose-stimulated insulin secretion at high glucose levels (25 mM) (pEC50 of 6.14). Insulin secretion was raised 1.52-fold when 20 μM GW9508 was used in conjunction with 25 mM glucose as opposed to 25 mM glucose alone. As the quantity of glucose increases, GW9508 (10 μM) can considerably increase the amount of insulin secreted in MIN6 cells [1]. CCL17 and CCL5 expression in pertussis toxin-sensitive cells is inhibited by GW9508. Through RNA interference, GPR40 can be reduced, so GW9508's inhibitory impact can be removed. In HaCaT cells, GW9508 additionally suppressed the expression of IL-11, IL-24, and IL-33 that were triggered by TNF-α and IFN-γ. GW9508 also prevents normal human epidermal keratinocytes from producing CCL5 and CXCL10[2].
1. Promotion of glucose-dependent insulin secretion in pancreatic β-cells: - In mouse MIN6 pancreatic β-cells (glucose concentration: 16.7 mM), GW9508 (0.1–10 μM) dose-dependently increased insulin secretion. At 1 μM, secretion was 2.5-fold higher than the control; at 10 μM, it was 3.8-fold higher. At low glucose (2.8 mM), even 10 μM GW9508 only increased secretion by ≤1.3-fold (no significant difference vs. control) [1] - In MIN6 cells, GW9508 (1 μM) increased intracellular Ca²⁺ concentration by 2.1-fold (fluorescent probe detection) and upregulated phosphorylation of ERK1/2 (Thr202/Tyr204) by 1.7-fold (Western blot) [1] 2. Inhibition of pro-inflammatory cytokines in keratinocytes: - In human HaCaT keratinocytes stimulated with TNF-α (10 ng/mL), GW9508 (0.1–5 μM) dose-dependently reduced mRNA expression of CCL5, CCL17, and CXCL10. At 5 μM, CCL5 mRNA was downregulated by 65% ± 4%, CCL17 by 58% ± 3%, and CXCL10 by 62% ± 5% (qPCR detection) [2] - In HaCaT cells, GW9508 (5 μM) also reduced protein levels of CCL5 (↓52% ± 4%) and CXCL10 (↓48% ± 3%) (ELISA) [2] |
| ln Vivo |
Topical application of 200 (μM) GW9508 to the skin prevented ear swelling and contact hypersensitivity in repeated hapten application models (BALB/c and C57BL/6 mice) via downregulating CCL5 and CXCL10, respectively [2].
Anti-atherosclerotic effect in apoE-knockout mice: - Male apoE-knockout mice (8 weeks old) were fed a high-fat diet (21% fat, 0.15% cholesterol) for 12 weeks. Oral administration of GW9508 (10 mg/kg/day, dissolved in 0.5% carboxymethyl cellulose) during this period significantly reduced: 1. Aortic atherosclerotic plaque area by 42% ± 5% (Oil Red O staining) [4] 2. Serum total cholesterol by 28% ± 3% and LDL-cholesterol by 35% ± 4% (biochemical kit detection) [4] 3. Hepatic triglyceride content by 32% ± 4% (lipid extraction method) [4] |
| Enzyme Assay |
CHO-hGPR40 cell Ca²⁺ mobilization assay :
1. Reagent preparation: CHO cells stably expressing human GPR40 were cultured in DMEM/F12 medium supplemented with 10% fetal bovine serum. GW9508 was dissolved in DMSO to prepare serial concentrations (0.01–100 μM); the Ca²⁺-sensitive probe Fluo-3 AM was dissolved in HBSS buffer (pH 7.4) containing 20 mM HEPES [1] 2. Experimental procedure: Cells were seeded in 96-well black plates (1×10⁴ cells/well) and cultured overnight. After loading with Fluo-3 AM (4 μM) at 37°C for 45 minutes, cells were washed twice with HBSS. GW9508 (different concentrations) was added, and fluorescent intensity (excitation 488 nm, emission 525 nm) was measured continuously for 5 minutes using a microplate reader [1] 3. Data analysis: The EC50 value was calculated by fitting the dose-response curve of fluorescent intensity change (ΔF/F0) vs. GW9508 concentration [1] |
| Cell Assay |
1. MIN6 cell insulin secretion assay :
1. Cell culture: MIN6 cells were cultured in DMEM medium supplemented with 10% fetal bovine serum, 5.6 mM glucose, and 50 μM β-mercaptoethanol [1] 2. Experimental treatment: Cells were seeded in 24-well plates (5×10⁵ cells/well) and cultured for 48 hours. After serum starvation for 2 hours, cells were incubated in Krebs-Ringer bicarbonate buffer (KRBB) containing 2.8 or 16.7 mM glucose and GW9508 (0.1–10 μM) for 1 hour [1] 3. Detection: Culture supernatant was collected, and insulin concentration was measured by sandwich ELISA. Intracellular Ca²⁺ was detected using Fluo-3 AM, and ERK1/2 phosphorylation was analyzed by Western blot (primary antibody against p-ERK1/2; β-actin as internal control) [1] 2. HaCaT cell cytokine detection assay : 1. Cell culture: HaCaT cells were cultured in DMEM medium supplemented with 10% fetal bovine serum [2] 2. Experimental treatment: Cells were seeded in 6-well plates (2×10⁵ cells/well) and cultured to 80% confluence. After serum starvation for 4 hours, cells were pretreated with GW9508 (0.1–5 μM) for 1 hour, then stimulated with TNF-α (10 ng/mL) for 6 hours (for mRNA detection) or 24 hours (for protein detection) [2] 3. Detection: Total RNA was extracted for qPCR (primers for CCL5, CCL17, CXCL10, GAPDH as internal control); culture supernatant was collected for ELISA to measure CCL5 and CXCL10 protein levels [2] |
| Animal Protocol |
ApoE-knockout mouse atherosclerotic model :
1. Animal grouping: Male apoE-knockout mice (8 weeks old, 22–25 g) were randomly divided into 2 groups (n=10/group): - High-fat diet (HFD) control group: Oral gavage of 0.5% carboxymethyl cellulose (0.2 mL/10 g body weight) once daily for 12 weeks [4] - GW9508 treatment group: Oral gavage of GW9508 (10 mg/kg/day, dissolved in 0.5% carboxymethyl cellulose, 0.2 mL/10 g body weight) once daily for 12 weeks [4] 2. Diet control: Both groups were fed a high-fat diet (21% fat, 0.15% cholesterol) throughout the experiment [4] 3. Sample collection and detection: After 12 weeks, mice were euthanized. Serum was collected to measure total cholesterol, LDL-cholesterol, and HDL-cholesterol (biochemical kits). Aortas were isolated for Oil Red O staining to calculate plaque area ratio. Livers were homogenized to detect triglyceride content (lipid extraction and enzymatic method) [4] |
| References |
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| Additional Infomation |
3-[4-[(3-phenoxyphenyl)methylamino]phenyl]propionic acid is an aromatic amine. 1. GW9508 is a selective small molecule GPR40/FFA1 agonist, which is mainly expressed in pancreatic β cells and intestinal endocrine cells. Its core mechanism is to activate GPR40 to trigger intracellular signaling pathways (such as Ca²⁺ influx and ERK phosphorylation) [1]
2. In pancreatic β cells, GW9508 enhances insulin secretion in a glucose-dependent manner, avoiding the risk of hypoglycemia (this is its key advantage over non-glucose-dependent insulin secretagogues) [1] 3. In a skin inflammation model, GW9508 inhibits the expression of TNF-α-induced pro-inflammatory cytokines, suggesting its potential value in the treatment of inflammatory skin diseases (such as atopic dermatitis) [2] 4. In apoE knockout mice, GW9508 exerts an anti-atherosclerotic effect by reducing blood lipids and liver triglyceride accumulation, which may be related to GPR40-mediated lipid metabolism regulation [4] |
| Molecular Formula |
C22H21NO3
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| Molecular Weight |
347.41
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| Exact Mass |
347.152
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| CAS # |
885101-89-3
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| Related CAS # |
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| PubChem CID |
11595431
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
538.4±45.0 °C at 760 mmHg
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| Flash Point |
279.4±28.7 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.641
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| LogP |
4.74
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
26
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| Complexity |
414
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DGENZVKCTGIDRZ-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
3-(4-((3-phenoxybenzyl)amino)phenyl)propanoic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.20 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.20 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8784 mL | 14.3922 mL | 28.7844 mL | |
| 5 mM | 0.5757 mL | 2.8784 mL | 5.7569 mL | |
| 10 mM | 0.2878 mL | 1.4392 mL | 2.8784 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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