Activation of Free Fatty Acid Receptor 4 Affects Intestinal Inflammation and Improves Colon Permeability in Mice was written by Salaga, Maciej;Bartoszek, Adrian;Binienda, Agata;Krajewska, Julia B.;Fabisiak, Adam;Mosinska, Paula;Dziedziczak, Katarzyna;Niewinna, Karolina;Talar, Marcin;Tarasiuk, Aleksandra;Kordek, Radzislaw;Fichna, Jakub. And the article was included in Nutrients in 2021.Safety of 2-(4-Chlorophenyl)-3-methyl-N-(thiazol-2-yl)butanamide This article mentions the following:
Diet is considered an important trigger in inflammatory bowel diseases (IBD), as feeding habits can affect intestinal permeability and clearance of bacterial antigens, consequently influencing the immune system. Free fatty acid receptors (FFARs), expressed on the intestinal epithelial cells, belong to the family of luminal-facing receptors that are responsive to nutrients. The objective of this study was to characterize the anti-inflammatory activity and the effect on intestinal barrier function of synthetic FFAR agonists in mouse models of colitis. Therapeutic activity of GW9508 (FFAR1 agonist), 4-CMTB (FFAR2 agonist), AR420626 (FFAR3 agonist), and GSK137647 (FFAR4 agonist) was investigated in two models of semi-chronic colitis: induced by trinitrobenzenesulfonic acid (TNBS), mimicking Crohn’s disease, as well as induced by dextran sulfate sodium (DSS), which recapitulates ulcerative colitis in humans. Moreover, we assessed the influence of FFARs agonists on epithelial ion transport and measured the ion flow stimulated by forskolin and veratridine. Administration of FFAR4 agonist GSK137647 attenuated both TNBS-induced and DSS-induced colitis in mice, as indicated by macroscopic parameters and myeloperoxidase activity. The action of FFAR4 agonist GSK137647 was significantly blocked by pretreatment with selective FFAR4 antagonist AH7614. Moreover, FFAR1 and FFAR4 agonists reversed the increase in the colon permeability caused by inflammation. FFAR4 restored the tight junction genes expression in mouse colon. This is the first evaluation of the anti-inflammatory activity of selective FFAR agonists, showing that pharmacol. intervention targeting FFAR4, which is a sensor of medium and long chain fatty acids, attenuates intestinal inflammation. In the experiment, the researchers used many compounds, for example, 2-(4-Chlorophenyl)-3-methyl-N-(thiazol-2-yl)butanamide (cas: 300851-67-6Safety of 2-(4-Chlorophenyl)-3-methyl-N-(thiazol-2-yl)butanamide).
2-(4-Chlorophenyl)-3-methyl-N-(thiazol-2-yl)butanamide (cas: 300851-67-6) belongs to thiazole derivatives. The thiazole ring has been identified as a central feature of numerous natural products, perhaps the most famous example of which is epothilone. There are numerous natural products that possess a thiazole ring with broad pharmacological activities. Thiamine, also known as vitamin B1, possesses a thiazole ring linked with 2-methylpyrimidine-4-amine as hydrochloride salt.Safety of 2-(4-Chlorophenyl)-3-methyl-N-(thiazol-2-yl)butanamide
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica