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TAK-875

现货
Catalog No.
A8339
GPR40激动剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,500.00
现货
5mg
¥ 1,200.00
现货
10mg
¥ 2,200.00
现货
50mg
¥ 4,700.00
Ship with 10-15 days

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Background

TAK-875 is a potent, selective, and oral GPR40 agonist. GPR40 is one of the G protein-coupled receptors predominantly expressed in pancreatic β-cells, mediating enhancement of glucose-stimulated insulin secretion by free fatty acids.

In vitro: TAK-875 exhibited potent agonist activity and high binding affinity to the human receptor. In addition, TAK-875 showed excellent agonist potency selectivity for GPR40 receptor over other members of the FFA receptor family (for which EC50>10 μM) [1].

In vivo: TAK-875 showed potent plasma glucose-lowering action and insulinotropic action during an oral glucose tolerance test in female Wistar fatty rats with impaired glucose tolerance [2].

Clinical trial: TAK-875 acts as a glucose-dependent insulinotropic agent with low hypoglycemic risk. Its P K is suitable for once-daily oral administration.

References:
[1] Negoro N, Sasaki S, Mikami S, Ito M, Suzuki M, Tsujihata Y, Ito R, Harada A, Takeuchi K, Suzuki N, Miyazaki J, Santou T, Odani T, Kanzaki N, Funami M, Tanaka T1, Kogame A, Matsunaga S, Yasuma T, Momose Y.  Discovery of TAK-875: A Potent, Selective, and Orally Bioavailable GPR40 Agonist. ACS Med Chem Lett. 2010 Jun 18;1(6):290-4.
[2] Leifke E, Naik H, Wu J, Viswanathan P, Demanno D, Kipnes M, Vakilynejad M.  A multiple-ascending-dose study to evaluate safety, pharmacokinetics, and pharmacodynamics of a novel GPR40 agonist, TAK-875, in subjects with type 2 diabetes. Clin Pharmacol Ther. 2012 Jul;92(1):29-39.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt524.64
Cas No.1000413-72-8
FormulaC29H32O7S
SynonymsTAK 875;TAK875
Solubility≥26.25mg/mL in DMSO
Chemical Name2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid
SDFDownload SDF
Canonical SMILESCC1=CC(=CC(=C1C2=CC(=CC=C2)COC3=CC4=C(C=C3)C(CO4)CC(=O)O)C)OCCCS(=O)(=O)C
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

激酶实验 [1]:

表达人GPR40 CHO细胞的Ca内流活性(FLIPR 试验)

将稳定表达人GPR40的CHO细胞接种,将其置5% CO2中,于37 °C下培养过夜。然后,将细胞置于加样缓冲液(记录培养液含2.5 μg/mL荧光钙指示剂Fluo 4-AM,2.5 mM丙磺舒和0.1%无脂肪酸的BSA)中,于37 ?C下培养60分钟。将不同浓度的TAK-875加入到细胞中,通过FLIPR Tsystem测定细胞内Ca2+浓度的增加量(90秒)。通过Prism 5软件得出TAK-875的EC50值。

动物实验 [1]:

动物模型

糖尿病大鼠模型

给药剂量

0.3 ~ 3 mg/kg,口服给药

实验结果

在糖尿病大鼠模型中,于口服葡萄糖耐量试验期间,单剂量TAK-87 (0.3 ~ 3 mg/kg) 减少血糖波动并增加胰岛素分泌。

其它注意事项

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]. Negoro N, Sasaki S, Mikami S, Ito M, Suzuki M, Tsujihata Y, Ito R, Harada A, Takeuchi K, Suzuki N, Miyazaki J, Santou T, Odani T, Kanzaki N, Funami M, Tanaka T1, Kogame A, Matsunaga S, Yasuma T, Momose Y. Discovery of TAK-875: A Potent, Selective, and Orally Bioavailable GPR40 Agonist. ACS Med Chem Lett. 2010 Jun 18;1(6):290-4.

生物活性

Description TAK-875是GPR40的选择性激动剂,其EC50为14 nM,比油酸效能高400倍。
靶点 GPR40          
IC50 14 nM (EC50)          

质量控制

化学结构

TAK-875

相关生物数据

TAK-875

相关生物数据

TAK-875