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.

Physicochemical Properties

Molecular Formula	C₁₆H₁₉NO₃S
Molecular Weight	305.39
Exact Mass	305.109
Elemental Analysis	C, 62.93; H, 6.27; N, 4.59; O, 15.72; S, 10.50
CAS #	349085-82-1
Related CAS #	349085-82-1
PubChem CID	743974
Appearance	White to off-white solid powder
LogP	4.575
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	21
Complexity	411
Defined Atom Stereocenter Count	0
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
InChi Key	FQUAFMNPXPXOJE-UHFFFAOYSA-N
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
Chemical Name	4-methoxy-N-(2,4,6-trimethylphenyl)benzenesulfonamide
Synonyms	GSK137647; GSK-137647; GSK 137647; GSK137647A; GSK-137647A; GSK 137647A
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	GPR120
ln Vitro	In vitro activity: GSK137647A (GSK 137647) (50 µM) lowers NO production in macrophages without impairing cell viability[1]. GSK137647A (GSK 137647) (30 µM; 12 hours) reduces the inflammatory response and promotes IL-6 secretion in Caco-2 cells[1]. GSK137647A (GSK 137647) (10 µM) impacts colonic epithelial ion transport and decreases ion flow in healthy individuals[1]. GSK137647A (GSK 137647) at 50 µM enhances the release of insulin stimulated by glucose[2].
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].
Cell Assay	Cell Line: Caco-2 cells Concentration: 30 µM Incubation Time: 12 hours Result: Downregulated FFAR1, FFAR2, and FFAR4 as compared to control.
Animal Protocol	Male C57BL/6 mice 1 mg/kg Intraperitoneal injection; twice daily, for 7 days
References	[1]. Activation of Free Fatty Acid Receptor 4 Affects Intestinal Inflammation and Improves Colon Permeability in Mice. Nutrients. 2021 Aug 6;13(8):2716. [2]. Identification of diarylsulfonamides as agonists of the free fatty acid receptor 4 (FFA4/GPR120). Bioorg Med Chem Lett. 2014 Jul 15;24(14):3100-3.

Solubility Data

Solubility (In Vitro)

DMSO: ~61 mg/mL (~199.7 mM) Water: N/A Ethanol: ~10 mg/mL

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.