4-CMTB is a selective free fatty acid receptor 2 (FFA2/GPR43) agonist and a positive allosteric modulator[1]. FFA2, also known as GPR43, is a G protein-coupled receptor activated by short-chain fatty acids that plays key roles in metabolism, immune regulation, and inflammatory responses[2]. 4-CMTB is usually used to study the mechanism of action of FFA2 receptors in inflammatory diseases, including asthma, colorectal cancer, intestinal ischemia-reperfusion injury, as well as metabolic diseases such as type 2 diabetes, obesity and insulin resistance[3][4].
In vitro, 4-CMTB (25μM; 48h) reduced cell viability, decreased cell migration and invasion, increased FFAR2/FFAR4 gene expression, yet decreased their protein levels in SW-480 cells[5].
In vivo, 4-CMTB (20mg/kg; i.p.; 30min before OVA challenge) inhibited OVA-induced immune cell accumulation in BALF and reduced mucin production in ovalbumin-induced allergic asthma BALB/c mice[6]. 4-CMTB (10mg/kg; i.p.; administered 30min before DNCB challenge) reversed DNCB-induced atopic dermatitis in BALB/c mice, suppressed ear epidermal hypertrophy, and reduced mast cell infiltration, serum IgE elevation and IL-4/IL-13 expression[7].
References:
[1] Smith NJ, Ward RJ, Stoddart LA, et al. Extracellular loop 2 of the free fatty acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator. Mol Pharmacol. 2011;80(1):163-173.
[2] Bindels LB, Dewulf EM, Delzenne NM. GPR43/FFA2: physiopathological relevance and therapeutic prospects. Trends Pharmacol Sci. 2013;34(4):226-232.
[3] Brown AJ, Tsoulou C, Ward E, et al. Pharmacological properties of acid N-thiazolylamide FFA2 agonists. Pharmacol Res Perspect. 2015;3(3):e00141.
[4] Lorza-Gil E, Kaiser G, Rexen Ulven E, et al. FFA2-, but not FFA3-agonists inhibit GSIS of human pseudoislets: a comparative study with mouse islets and rat INS-1E cells. Sci Rep. 2020;10(1):16497.
[5] Binienda A, Owczarek K, Sałaga M, Fichna J. Synthetic free fatty acid receptor (FFAR) 2 agonist 4-CMTB and FFAR4 agonist GSK13764 inhibit colon cancer cell growth and migration and regulate FFARs expression in in vitro and in vivo models of colorectal cancer. Pharmacol Rep. 2024;76(6):1403-1414.
[6] Lee JH, Im DS. 4-CMTB Ameliorates Ovalbumin-Induced Allergic Asthma through FFA2 Activation in Mice. Biomol Ther (Seoul). 2021;29(4):427-433.
[7] Kang J, Im DS. FFA2 Activation Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice. Biomol Ther (Seoul). 2020;28(3):267-271.
4-CMTB是一种选择性的游离脂肪酸受体2（FFA2/GPR43）激动剂和正变构调节剂[1]。FFA2，也称为GPR43，是一种由短链脂肪酸激活的G蛋白偶联受体，在代谢、免疫调节和炎症反应中发挥关键作用[2]。4-CMTB通常用于研究FFA2受体在炎症性疾病（包括哮喘、结直肠癌、肠缺血再灌注损伤）以及2型糖尿病、肥胖和胰岛素抵抗等代谢性疾病中的作用机制[3][4]。
体外实验中，4-CMTB（25μM；48小时）降低了SW-480细胞的活力，抑制细胞迁移和侵袭，增加FFAR2/FFAR4基因表达，但降低了它们的蛋白水平[5]。
体内实验中，4-CMTB（20mg/kg；腹腔注射；OVA刺激前30分钟）抑制了卵清蛋白诱导的过敏性哮喘BALB/c小鼠的BALF中免疫细胞积聚，并减少了黏蛋白的产生[6]。4-CMTB（10mg/kg；腹腔注射；DNCB刺激前30分钟给药）逆转了DNCB诱导的BALB/c小鼠特应性皮炎，抑制了耳部表皮增生，并减少了肥大细胞浸润、血清IgE升高以及IL-4/IL-13的表达[7]。