GSK3 Inhibitor XV
目录号 : GC43791
GSK3 inhibitor XV 是 (R)-GSK3 inhibitor XV 和 (S)-GSK3 inhibitor XV 的外消旋混合物。
Cas No.:936112-69-5
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
GSK3 inhibitor XV is a racemic mixture of (R)-GSK3 inhibitor XV and (S)-GSK3 inhibitor XV. (R)-GSK3 inhibitor XV inhibits glycogen synthase kinase (GSK) 3α and β (IC50s = 0.35 and 0.55 nM, respectively). It selectively inhibits GSK3α and β over a kinase panel including MSK1, RSK1, and TRKA (IC50s = 3,000, 8,000, and 350 nM, respectively), however, it also inhibits PIM-1 with an IC50 value of 35 nM. (R)-GSK3 inhibitor XV (1 μM) disrupts development of the anterior and posterior termini in zebrafish embryos. (S)-GSK3 inhibitor XV is less potent than the (R)-enantiomer, is selective for PIM-1 over GSK3 (IC50s = 3, 80, and 90 nM for PIM-1, GSK3α, and GSK3β, respectively), and has no effect on zebrafish embryonic development.
| Cas No. | 936112-69-5 | SDF | |
| Canonical SMILES | [O]#C[Ru+2]12345([N]6=C(C(Br)=CC(O)=C7)C7=C8C6=C9[N-]5C=CC=C9C(C%10=O)=C8C(N%10)=O)[C-]%11(C(OC)=O)[CH]1=[CH]2[CH]3=[CH]4%11 | ||
| 分子式 | C25H14BrN3O6Ru | 分子量 | 633.4 |
| 溶解度 | Soluble 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5788 mL | 7.8939 mL | 15.7878 mL |
| 5 mM | 0.3158 mL | 1.5788 mL | 3.1576 mL |
| 10 mM | 0.1579 mL | 0.7894 mL | 1.5788 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。
Analysis of Glycogen Synthase Kinase Inhibitors That Regulate Cytochrome P450 Expression in Primary Human Hepatocytes by Activation of β-Catenin, Aryl Hydrocarbon Receptor and Pregnane X Receptor Signaling
Toxicol Sci 2015 Nov;148(1):261-75.PMID:26259606DOI:10.1093/toxsci/kfv177.
Cytochrome P450 (CYP) expression and activity are not homogeneous in the liver lobules. Indeed, CYPs are mainly expressed and induced in centrilobular hepatocytes. The wingless-type MMTV integration site family (WNT)/β-catenin pathway was identified as a major regulator of this zonal organization. We have recently demonstrated that in primary human hepatocytes (PHHs), the expression of CYP2E1, CYP1A2, and aryl hydrocarbon receptor (AhR), but not of CYP3A4, is regulated by the WNT/β-catenin pathway in response to WNT3a, its canonical activator. Here, we investigated whether glycogen synthase kinase 3β (GSK3β) inhibitors, which mimic the action of WNT molecules, could be used in PHHs to activate the β-catenin pathway to study CYP expression. We assessed the activity of 6BIO (6-bromoindirubin-3'-oxime), CHIR99021 (6-((2-((4-(2,4-dichlorophenyl)-5-(4methyl-1H-imidazol-2-yl)pyrimidin-2-yl)amino)ethyl)amino) nicotinonitrile), and GSK3iXV (Pyridocarbazolo-cyclopentadienyl Ruthenium complex GSK3 Inhibitor XV) that belong to structurally different families of GSK3β inhibitors. Using small interfering RNAs, reporter gene assays, and molecular docking predictions, we demonstrated that GSK3β inhibitors can activate the WNT/β-catenin pathway in PHHs to regulate CYP2E1 expression. We also found that 6BIO and GSK3iXV are AhR full agonists that participate, through AhR signaling, to CYP1A2 induction. Conversely, CHIR99021 is an AhR partial agonist, and a pregnane X receptor ligand and partial agonist, thus regulating CYP1A2 and CYP3A4 gene expression in a β-catenin-independent manner. In conclusion, GSK3β inhibitors can activate the WNT/β-catenin pathway in PHHs. Nevertheless, their role in CYP regulation should be analyzed with caution as these molecules can interact with xenosensors.