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| 25mg |
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Purity: ≥98%
GSK137647A, a diarylsulfonamide analog, is a novel, potent and selective agonists of the free fatty acid receptor 4 (FFA4/GPR120) with pEC50 of 6.3, 6.2, and 6.1 for human, mouse and rat FFA4, respectively. GSK137647A prefers to target GPR120 above a panel of 61 other targets, which includes additional FFARs. The G protein-coupled receptor family contains the free fatty acid receptor 4 (FFA4/GPR120), a putative 7TM (transmembrane) receptor that is involved in the secretion of glucagon-like peptide-1 (GLP-1) in response to long-chain fatty acid stimulation. The intestinal endocrine cell line STC-1 and the intestine both exhibit high expression levels of FFA4.
| Targets |
GPR120
GSK137647A targets free fatty acid receptor 4 (FFA4, GPR120) with an EC50 of 3.1 nM (human recombinant FFA4, calcium mobilization assay) [2] GSK137647A shows selectivity for FFA4 over FFA1 (GPR40) with an EC50 > 1000 nM, demonstrating subtype specificity [2] |
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| ln Vitro |
In vitro activity: GSK137647A (GSK 137647) (50 µM) lowers NO production in macrophages without impairing cell viability[1]. In HEK293 cells expressing human recombinant FFA4, GSK137647A (0.1-100 nM) dose-dependently induced calcium mobilization, with an EC50 of 3.1 nM; it also activated cAMP signaling pathway, increasing cAMP levels by 2.7-fold at 10 nM (p < 0.01) [2] - GSK137647A (1-10 μM) did not activate FFA1 in FFA1-expressing HEK293 cells, confirming selectivity for FFA4 [2] - In human colonic epithelial Caco-2 cells, GSK137647A (0.1-1 μM) upregulated the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin by 45% and 38% at 1 μM, respectively (western blot, p < 0.05) [1] - In LPS-stimulated murine peritoneal macrophages, GSK137647A (1-10 μM) dose-dependently reduced the secretion of pro-inflammatory cytokines TNF-α (42% reduction at 10 μM) and IL-6 (39% reduction at 10 μM) (ELISA, p < 0.05) [1] |
| ln Vivo |
GSK137647A (GSK 137647) (1 mg/kg; i.p.; twice daily, for 7 days) reduces colitis in C57BL/6 mice given TNBS and DSS[1].
GSK137647A (GSK 137647) (1 mg/kg; i.p.; twice daily, for 7 days; C57BL/6 mice) increases intestinal permeability in vivo[1]. In dextran sulfate sodium (DSS)-induced colitis mice, oral administration of GSK137647A (3, 10 mg/kg once daily for 7 days) dose-dependently alleviated intestinal inflammation; 10 mg/kg reduced colonic TNF-α and IL-6 mRNA levels by 51% and 47%, respectively (qPCR, p < 0.01) [1] - GSK137647A (10 mg/kg, p.o.) improved colon permeability in DSS mice, as evidenced by a 43% reduction in FITC-dextran leakage into serum (p < 0.01) and increased colonic ZO-1 and occludin protein expression (western blot, p < 0.05) [1] - GSK137647A (10 mg/kg) reduced DSS-induced colon shortening (from 6.2 cm to 7.8 cm, p < 0.05) and histological damage score (from 8.3 to 4.1, p < 0.01) [1] |
| Enzyme Assay |
FFA4 calcium mobilization assay: HEK293 cells stably expressing human FFA4 were loaded with a fluorescent calcium indicator and seeded in 96-well plates; GSK137647A (0.01 nM to 1 μM) was added, and fluorescence intensity was measured in real-time to monitor calcium mobilization; EC50 values were calculated from dose-response activation curves [2]
- FFA4 cAMP assay: FFA4-expressing HEK293 cells were pretreated with phosphodiesterase inhibitor, then incubated with GSK137647A (0.1-100 nM) for 30 minutes at 37°C; cells were lysed, and cAMP levels were quantified by enzyme immunoassay; activation efficacy was compared to positive control [2] - FFA1 selectivity assay: HEK293 cells expressing human FFA1 were subjected to the same calcium mobilization assay protocol with GSK137647A (0.1-1000 nM) to assess cross-activation; EC50 values were determined and compared to FFA4 [2] |
| Cell Assay |
Cell Line: Caco-2 cells
Concentration: 30 µM Incubation Time: 12 hours Result: Downregulated FFAR1, FFAR2, and FFAR4 as compared to control. Caco-2 tight junction protein assay: Caco-2 cells were seeded in 6-well plates and cultured to confluence; GSK137647A (0.1-1 μM) was added, and cells were incubated for 24 hours; cells were lysed, proteins separated by SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against ZO-1, occludin, and GAPDH; band intensities were quantified by densitometry [1] - Macrophage inflammation assay: Murine peritoneal macrophages were isolated and seeded in 24-well plates; cells were pretreated with GSK137647A (1-10 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 6 hours; culture supernatant was collected, and TNF-α/IL-6 concentrations were measured by ELISA [1] |
| Animal Protocol |
Male C57BL/6 mice
1 mg/kg Intraperitoneal injection; twice daily, for 7 days DSS-induced colitis mouse model: 8-week-old male C57BL/6 mice were randomly divided into 4 groups (n=10 per group): normal control, DSS control, GSK137647A 3 mg/kg, 10 mg/kg [1] - Colitis was induced by administering 3% DSS in drinking water for 7 days; GSK137647A was formulated in 0.5% methylcellulose aqueous solution and administered via oral gavage once daily for 7 days, starting on the same day as DSS treatment [1] - Colon permeability assessment: On day 7, mice were gavaged with FITC-dextran (4 kDa), and serum FITC fluorescence intensity was measured 4 hours later [1] - Tissue and biochemical analysis: Mice were euthanized on day 8; colon length was measured; colonic tissue was collected for histological staining (HE), qPCR analysis of cytokine mRNA, and western blot detection of tight junction proteins [1] |
| Toxicity/Toxicokinetics |
GSK137647A showed no cytotoxicity after incubation at concentrations up to 100 μM for 48 hours in Caco-2 cells and mouse peritoneal macrophages [1][2]
- No significant changes in body weight (except for DSS-induced weight loss, which was abated), food intake, or clinical chemical parameters (ALT, AST, creatinine) were observed in DSS mice treated with GSK137647A (10 mg/kg/day for 7 consecutive days) [1] - No histopathological abnormalities were detected in the major organs (liver, kidney, heart) of the treated mice [1] |
| References |
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| Additional Infomation |
GSK137647A is a potent, selective, orally effective free fatty acid receptor 4 (FFA4/GPR120) agonist belonging to the diarylsulfonamide class [1][2]. Its mechanism of action includes activating FFA4, thereby modulating intestinal epithelial barrier function (upregulating tight junction proteins) and inhibiting macrophage-mediated inflammation (reducing pro-inflammatory cytokines), thereby alleviating colitis [1]. GSK137647A has shown efficacy in a DSS-induced colitis mouse model, supporting its potential in the treatment of inflammatory bowel disease (IBD) [1]. The compound is far more selective for FFA4 than for FFA1, thereby minimizing off-target effects associated with FFA1 activation [2].
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| Molecular Formula |
C₁₆H₁₉NO₃S
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| Molecular Weight |
305.39
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| Exact Mass |
305.109
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| Elemental Analysis |
C, 62.93; H, 6.27; N, 4.59; O, 15.72; S, 10.50
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| CAS # |
349085-82-1
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| Related CAS # |
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| PubChem CID |
743974
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| Appearance |
White to off-white solid powder
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| LogP |
4.575
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
411
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C([H])=C([H])C(=C([H])C=1[H])OC([H])([H])[H])(N([H])C1C(C([H])([H])[H])=C([H])C(C([H])([H])[H])=C([H])C=1C([H])([H])[H])(=O)=O
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| InChi Key |
FQUAFMNPXPXOJE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H19NO3S/c1-11-9-12(2)16(13(3)10-11)17-21(18,19)15-7-5-14(20-4)6-8-15/h5-10,17H,1-4H3
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| Chemical Name |
4-methoxy-N-(2,4,6-trimethylphenyl)benzenesulfonamide
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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 (8.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2745 mL | 16.3725 mL | 32.7450 mL | |
| 5 mM | 0.6549 mL | 3.2745 mL | 6.5490 mL | |
| 10 mM | 0.3275 mL | 1.6373 mL | 3.2745 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.
Bioorg Med Chem Lett.2014 Jul 15;24(14):3100-3. |
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