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INT-777

现货
Catalog No.
B4672
TGR5受体激动剂
组合的产品项目
规格价格库存 数量
5mg
¥ 4,200.00
现货

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Background

INT-777 (S-EMCA) is a potent and selective agonist of TGR5 receptor with EC50 value of 0.82 μM [1].

TGR5 receptor is a G protein-coupled receptor and functions as a cell surface receptor for bile acids. TGR5 receptor plays an important role in the regulation of energy homeostasis by bile acids and suppression of macrophage functions [1].

INT-777 (S-EMCA) is a potent and selective TGR5 receptor agonist [1]. In macrophages, INT-777 inhibited proinflammatory cytokine production by TGR5-induced cAMP signaling and subsequent NF-kB inhibition [2]. In pancreatic β cell line MIN6, INT-777 selectively activated Gαs and increased intracellular cAMP and Ca2+. INT-777 also increased phosphoinositide (PI) hydrolysis and insulin release, which was dependent on Gs/cAMP/Ca2+ pathway [3]. In human podocytes with high glucose, INT-777 induced mitochondrial biogenesis, increased fatty acid β-oxidation and decreased oxidative stress [4].

In Ldlr- /- Tgr5+/+ mice, INT-777 activated TGR5 and attenuated atherosclerosis, which was associated with less plaque macrophage content and decreased intraplaque inflammation [2]. In diabetic db/db mice, INT-777 decreased mitochondrial H2O2 production and increased SOD2 activity, then reduced proteinuria, mesangial expansion, podocyte injury, fibrosis, and CD68 macrophage infiltration in the kidney [4].

References:
[1].  Pellicciari R, Gioiello A, Macchiarulo A, et al. Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity. J Med Chem, 2009, 52(24): 7958-7961.
[2].  Pols TW, Nomura M, Harach T, et al. TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading. Cell Metab, 2011, 14(6): 747-757.
[3].  Kumar DP, Rajagopal S, Mahavadi S, et al. Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic β cells. Biochem Biophys Res Commun, 2012, 427(3): 600-605.
[4].  Wang XX, Edelstein MH, Gafter U, et al. G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in Obesity and Diabetes. J Am Soc Nephrol, 2015. pii: ASN.2014121271.

Chemical Properties

Physical AppearanceA crystalline solid
StorageStore at -20°C
M.Wt450.65
Cas No.1199796-29-6
FormulaC27H46O5
SolubilitySoluble in DMSO
SDFDownload SDF
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验: [1]

细胞系

RAW264.7细胞

制备方法

溶解度有限,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

37℃

实验结果

组合的LPS-INT-777处理显著减弱Tnfa、单核细胞趋化蛋白1(Mcp-1)、Il-6和Il-1b的mRNA水平的瞬时增加。INT-777通过激活TGR5,显著减少p65易位,c-Jun的磷酸化未改变。

动物实验: [1]

动物模型

TGR5基因模型

给药剂量

30 mg/kg/day.

实验结果

INT-777通过激活白细胞中的TGR5,抑制动脉粥样硬化。在移植有Tgr5+/+小鼠骨髓的Ldlr-/-小鼠中,INT-777引起较少的血管损伤,表明INT-777对动脉粥样硬化的发展产生抑制作用。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

1. Pols TW, Nomura M, Harach T et al. TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading. Cell Metab. 2011 Dec 7;14(6):747-57.

质量控制

质量控制和MSDS

批次:

化学结构

INT-777