TAK-875
(Synonyms: TAK 875;TAK875) 目录号 : GC16555
A selective FFAR1 (GPR40) agonist
Cas No.:1000413-72-8
Sample solution is provided at 25 µL, 10mM.
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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.
| Kinase experiment [1]: | |
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Ca influx activity of CHO cells expressing human GPR40 (FLIPR assay) |
CHO cells stably expressing human GPR40 were plated and incubated overnight in 5% CO2 at 37 °C. Then, cells were incubated in loading buffer (recording medium containing 2.5 μg/mL fluorescent calcium indicator Fluo 4-AM, 2.5 mM probenecid and 0.1% fatty acid-free BSA) for 60 mins at 37 ?C. Various concentrations of TAK-875 were added into the cells and increase of the intracellular Ca2+ concentration after addition was monitored by FLIPR Tsystem for 90 seconds. EC50 value of TAK-875 was obtained with Prism 5 software. |
| Animal experiment [1]: | |
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Animal models |
A rat model of diabetes |
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Dosage form |
0.3 ~ 3 mg/kg, p.o. |
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Applications |
In a rat model of diabetes, single dose of TAK-875 at 0.3 ~ 3 mg/kg reduced the blood glucose excursion and increased insulin secretion during an oral glucose tolerance test. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
| Cas No. | 1000413-72-8 | SDF | |
| 别名 | TAK 875;TAK875 | ||
| 化学名 | 2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid | ||
| Canonical SMILES | CC1=CC(=CC(=C1C2=CC(=CC=C2)COC3=CC4=C(C=C3)C(CO4)CC(=O)O)C)OCCCS(=O)(=O)C | ||
| 分子式 | C29H32O7S | 分子量 | 524.64 |
| 溶解度 | ≥ 26.25mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9061 mL | 9.5303 mL | 19.0607 mL |
| 5 mM | 0.3812 mL | 1.9061 mL | 3.8121 mL |
| 10 mM | 0.1906 mL | 0.953 mL | 1.9061 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet