CHIR-99021 (CT99021)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
CHIR-99021是一种高特异性的糖原合酶激酶-3（GSK-3）抑制剂，抑制GSK-3α和GSK-3β，IC50值分别为10 nM和6.7 nM。
CHIR-99021通过稳定下游效应子，如c-Myc和β-catenin，从而促进B6和BALB/c ES细胞的自我更新，维持细胞多能性[1]。在J1 mESC细胞中，CHIR-99021与白血病抑制因子（LIF）联合使用时，在维持集落形态及自我更新方面具有重要作用。CHIR-99021调控多种信号途径，涉及Wnt/β-catenin、TGF-β、Nodal和MAPK，也调控表观遗传调控基因，如Dnmt3l的表达[2]。
在缺乏预TCR信号、Notch1信号或CXCL12时，CHIR-99021促进DN3胸腺细胞的增殖和分化[3]。研究还发现，更高浓度的CHIR99021（10 μM，而非1 μM或3 μM）可能通过激活IL-7信号传导途径，从而选择性地抑制分化[3]。
参考文献：
1. Ye S1, Tan L, Yang R, Fang B, Qu S, Schulze EN, Song H, Ying Q, Li P. Pleiotropy of glycogen synthase kinase-3 inhibition by CHIR99021 promotes self-renewal of embryonic stem cells from refractory mouse strains. PLoS One. 2012;7(4):e35892.
2. Wu Y1, Ai Z, Yao K, Cao L, Du J, Shi X, Guo Z, Zhang Y. CHIR99021 promotes self-renewal of mouse embryonic stem cells by modulation of protein-encoding gene and long intergenic non-coding RNA expression. Exp Cell Res. 2013
3. PLoS One. 2013;8(3):e58501. doi: 10.1371/journal.pone.0058501. Epub 2013 Mar 20. Schroeder JH1, Bell LS, Janas ML, Turner M. Pharmacological inhibition of glycogen synthase kinase 3 regulates T cell development in vitro. PLoS One. 2013;8(3):e58501.
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| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 465.34 |
| Cas No. | 252917-06-9 |
| Formula | C22H18Cl2N8 |
| Synonyms | CHIR99021, CHIR-99021, CHIR 99021, CT99021,GSK-3 Inhibitor XVI |
| Solubility | ≥23.27 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| Chemical Name | 6-((2-((4-(2,4-dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)pyrimidin-2-yl)amino)ethyl)amino)nicotinonitrile |
| SDF | Download SDF |
| Canonical SMILES | N#CC1=CC=C(NCCNC2=NC=C(C3=NC=C(C)N3)C(C4=CC=C(Cl)C=C4Cl)=N2)N=C1 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验[1]: | |
|
细胞系 |
人类胚胎干细胞(ESCs) |
|
溶解方法 |
该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液，一般步骤如下：请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月 |
|
反应条件 |
8 μM，24小时 |
|
实验结果 |
在第0天，用8μMCHIR-99021起始分化24小时，赋予经典的Wnt/β-联蛋白活化，接着在第3天加入4μMIWR-1进行为期48小时的Wnt抑制。对于测试的所有组，在第6天观察到eGFP荧光的第一体征和第一次跳动EB，持续增加直到d10，对于接种了666-2000个细胞的实验组达到几乎100％的跳动EB。对于接种666个细胞/聚集体的组，在第10天解离的EB的流式细胞术分析显示5.9Nkx2-5-eGFP+细胞的最高产率；每个聚集体较高的细胞数目导致较低的产量。EB冷冻切片和解离/再接种细胞的免疫荧光染色证实了高含量的Nkx2-5+和cTnT+心肌细胞，从而证明了在琼脂糖微孔上聚集和用基于小分子的培养基诱导后，人ESC衍生EB的有效心肌分化。 |
| 动物实验[2]: | |
|
动物模型 |
秋田1型糖尿病小鼠和野生型小鼠 |
|
剂量 |
腹腔注射，每日50 mg/kg |
|
实验结果 |
在普萘洛尔注射后15分钟，2-min平均HF分数从CHIR-99021处理前的46.8 ± 2.9％增加到处理后的67.8 ± 5.1％。用CHIR-99021处理Akita小鼠使SREBP-1从0.53 ± 0.07增加到1.17 ± 0.11倍。野生型小鼠中，CHIR-99021治疗使GIRK4水平从0.28 ± 0.06增加至1.08 ± 0.14倍，显著高于安慰剂。 |
|
注意事项 |
请测试所有化合物在室内的溶解度，实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的，属于正常现象。 |
|
References: [1] Dahlmann J, Kensah G, Kempf H, et al. The use of agarose microwells for scalable embryoid body formation and cardiac differentiation of human and murine pluripotent stem cells. Biomaterials, 2013, 34(10): 2463-2471. [2] Zhang Y, Welzig C M, Picard K L, et al. Glycogen synthase kinase-3β inhibition ameliorates cardiac parasympathetic dysfunction in type 1 diabetic Akita mice. Diabetes, 2014, 63(6): 2097-2113. |
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| 描述 | CHIR-99021 (CT99021)是GSK-3α/β的抑制剂，IC50值为10 nM/6.7 nM，比对其最接近同系物CDC2和ERK2，以及其它蛋白激酶的选择性高500倍以上。 | |||||
| 靶点 | GSK-3 | |||||
| IC50 | 7 nM | |||||
质量控制和MSDS
- 批次：
化学结构
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