CHIR-98014
目录号 : GC12176
A reversible, cell-permeable inhibitor of GSK3
Cas No.:252935-94-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment: | |
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Cell lines |
Insulin receptor– expressing CHO-IR cells and primary rat hepatocytes |
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Preparation method |
The solubility of this compound in DMSO is |
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Reaction Conditions |
24h; EC50=106 nM (CHO-IR cells); EC50=107 nM (rat hepatocytes). |
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Applications |
CHIR 98014 resulted in a stimulation of the GS activity ratio above basal. The concentrations of CHIR 98014 causing half-maximal GS stimulation (EC50) were 106 nM for CHO-IR cells and 107 nM for rat hepatocytes. |
| Animal experiment: | |
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Animal models |
Female db/db mice. |
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Dosage form |
30 mg/kg; oral taken |
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Applications |
Markedly diabetic and insulin-resistant db/db mice treated with 30 mg/kg CHIR 98014 exhibited a significant reduction in fasting hyperglycemia within 4 h of treatment and showed improved glucose disposal during an IPGTT. |
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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] Ring D B, Johnson K W, Henriksen E J, et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo[J]. Diabetes, 2003, 52(3): 588-595. |
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CHIR-98014 is a potent inhibitor of GSK-3α and GSK-3β with IC50 values of 0.65 nM and 0.58 nM, respectively [1]
GSK-3 (Glycogen synthase kinase 3) is a serine/threonine protein kinase and plays a pivotal role in a number of central intracellular signaling pathways, including cellular proliferation, migration, inflammation and immune responses, glucose regulation, and apoptosis. Recently, it has been reported that GSK-3 abnormally expressed in a variety of diseases, including Type II diabetes, Alzheimer's Disease, inflammation, cancer, and bipolar disorder [2, 3].
CHIR-98014 is a potent GSK-3α and GSK-3β inhibitor. When tested with insulin receptor-expressing CHO-IR cells or primary rat hepatocytes, CHIR-98014 stimulated the GS activity ratio as high as two- to three fold compared with basal in a dose dependent manner. Similarly, in isolated type 1 skeletal muscle from insulin-sensitive lean Zucker and from insulin-resistant ZDF rats, administration of CHIR-98014 activated GS activity ratio [1]. In mouse ES-D3 cells, CHIR-98014 treatment (48 and 72 hours later) resulted in a significant activation of the Wnt/beta-catenin pathway via inhibiting GSK-3 [4].
In markedly diabetic and insulin-resistant db/db mice model, oral administration of CHIR-98014 (30mg/kg) significantly reduced fasting hyperglycemia within 4 hours and improved glucose disposal during an ipGTT [1].
References:
[1]. Ring, D.B., et al., Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes, 2003. 52(3): p. 588-95.
[2]. Pan WA, et al. The RNA recognition motif of NIFK is required for rRNA maturation during cell cycle progression. RNA Biol. 2015. 12(3):255-67.
[3]. McCubrey JA, et al. GSK-3 as potential target for therapeutic intervention in cancer. Oncotarget. 2014. 5(10):2881-911.
[4]. Naujok O, et al. Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors. BMC Res Notes. 2014. 7(1):273-281.
| Cas No. | 252935-94-7 | SDF | |
| 化学名 | 6-N-[2-[[4-(2,4-dichlorophenyl)-5-imidazol-1-ylpyrimidin-2-yl]amino]ethyl]-3-nitropyridine-2,6-diamine | ||
| Canonical SMILES | C1=CC(=C(C=C1Cl)Cl)C2=NC(=NC=C2N3C=CN=C3)NCCNC4=NC(=C(C=C4)[N+](=O)[O-])N | ||
| 分子式 | C20H17Cl2N9O2 | 分子量 | 486.31 |
| 溶解度 | ≥ 8.1mg/mL in DMSO with gentle warming | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0563 mL | 10.2815 mL | 20.563 mL |
| 5 mM | 0.4113 mL | 2.0563 mL | 4.1126 mL |
| 10 mM | 0.2056 mL | 1.0282 mL | 2.0563 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。