DC260126

An FFAR1 (GPR40) antagonist

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库存: 现货

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5mg

￥400.00

320.00

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10mg

￥625.00

500.00

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25mg

￥1262.00

1010.00

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货号: ajci20492
CAS: 346692-04-4
别名:
分子式: C16H18FNO2S
分子量: 307.4
纯度: >98%
溶解度: ≤100mg/ml in ethanol;20mg/ml in DMSO;30mg/ml in dimethyl formamide
储存: Store at -20°C
库存: 现货

Background

DC260126 is a GPR40 antagonist [1][2].

The G protein-coupled receptor 40 (GPR40), also known as FFAR1, is a free fatty acid receptor, which is activated by saturated and unsaturated long or medium chain fatty acids in pancreatic β-cells. Free fatty acids (FFAs) are essential regulators of normal β-cell and play important roles in the pathogenesis of β-cell dysfunction in type 2 diabetes. GPR40 is a new potential drug target for the treatment of type 2 diabetes [1][2].

DC260126 is a FFAR1/GPR40 antagonist. DC260126 dose-dependently inhibited GPR40-mediated Ca2+ elevations stimulated by linoleic acid, oleic acid, palmitoleic acid and lauric acid with IC50 values of 6.28 ± 1.14, 5.96 ± 1.12, 7.07 ± 1.42 and 4.58 ± 1.14 μM, respectively. In GPR40-CHO cells, DC260126 dose-dependently reduced GTP-loading and ERK1/2 phosphorylation stimulated by linoleic acid. In Min6 cells, DC260126 inhibited palmitic acid potentiated glucose-stimulated insulin secretion, and negatively regulated GPR40 mRNA expression induced by oleic acid [1].

In obese diabetic db/db mice, DC260126 (10 mg/kg, 21-days treatment) significantly inhibited glucose stimulated insulin secretion, reduced blood insulin level and improved insulin sensitivity. DC260126 also reduced the apoptotic rate of pancreatic β-cells and the proinsulin/insulin ratio [2].

参考文献:
[1].? Hu H, He LY, Gong Z, et al. A novel class of antagonists for the FFAs receptor GPR40. Biochem Biophys Res Commun. 2009 Dec 18;390(3):557-63.
[2].? Sun P, Wang T, Zhou Y, et al. DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice. PLoS One. 2013 Jun 11;8(6):e66744.

Protocol

Animal experiment:

Mice[1] Male C57BL/KsJ-Lepdb (db/db) are maintained in a 12 h light-dark cycle at a temperature of 23°C with free access to water and regular chow diet. To investigate the dose-dependent effect of DC260126, nine-week-old db/db male mice are divided into four groups (n=6/group). Mice are give vehicle (5% DMSO in PBS) or DC260126 (3, 10, 30 mg/kg) once daily by tail vein injection for 5 days. At day 5, each group of mice are fasted for 6 h and blood samples are collected from orbital venous plexus and centrifuged for serum separation. Then the concentration of serum insulin level is measured by ELISA kit. For long term experiments, six-week-old obese db/db male mice are divided into two groups (n=8/group) and given vehicle (5% DMSO in PBS) or DC260126 (10 mg/kg) once daily by tail vein injection for 24 days, respectively. Rats[2] Female obese (fa/fa) Zucker rats are maintained in a 12:12 light-dark cycle with free access to water and a high-fat diet containing 15% fat, 1% cholesterol, 0.5% sodium cholate and 15% sucrose, except when fasted before some experiments. Rats at 8 weeks of age are divided into two groups (n=6/group) on the basis of body weight. Rats are injected intraperitoneally once daily with vehicle (propylene glycol) or DC260126 (6 mg/kg) for 8 weeks. Food intake and body weight are monitored periodically. At the end of the experimental period, mice are fasted for 12 h and then blood is collected. Liver, renal, adipose tissues are rapidly excised and weighed. Liver samples are snap frozen in liquid nitrogen and stored at -80°C for western blotting analysis.

参考文献:

[1]. Sun P, et al. DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice. PLoS One. 2013 Jun 11;8(6):e66744.
[2]. Zhang X, et al. DC260126, a small-molecule antagonist of GPR40, improves insulin tolerance but not glucose tolerance in obese Zucker rats. Biomed Pharmacother. 2010 Nov;64(9):647-51.