CHIR 99021

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Chemical Structure| 252917-06-9 同义名 : CT99021;Laduviglusib
CAS号 : 252917-06-9
货号 : A133052
分子式 : C22H18Cl2N8
纯度 : 99%+
分子量 : 465.338
MDL号 : MFCD11846251
存储条件：

Pure form Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 16 mg/mL(34.38 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 55 mg/mL suspension

生物活性
靶点

  • GSK-3α

    GSK-3α, IC50:10 nM

  • GSK-3β

    GSK-3β, IC50:6.7 nM
描述 GSK-3 (Glycogen synthase kinase 3) is a serine/threonine protein kinase, consisting of GSK-3α andβsubunit, which plays a key role in many different biological processes including tumorigenesis, cell survival, and developmental patterning. GSK-3 is constitutively active in non-stimulated cells and can negatively regulate canonical Wnt/β-catenin signaling. CHIR 99021 （CT99021）is highly selective aminopyrimidine-derivatived inhibitor of GSK-3 with IC50 of 10nM and 6.7nM for GSK-3α and GSK-3β(measured by kinase assays), respectively, and exhibits >500-fold selectivity for GSK-3 over closely related kinases, such as cdc2[8]Bennett CN, Ross SE, Longo KA, Bajnok L, Hemati N, Johnson KW, Harrison SD, MacDougald OA. Regulation of Wnt signaling during adipogenesis. J Biol Chem. 2002 Aug 23;277(34):30998-1004. doi: 10.1074/jbc.M204527200. Epub 2002 Jun 7. PMID: 12055200. https://pubmed.ncbi.nlm.nih.gov/12055200/. CHIR-99021 can mimic Wnt signaling in preadipocytes. Analysis of cytosolic and membranous fractions show that the free cytosolic -catenin was evaluated in 3T3-L1 preadipocytes treated with 3uM CHIR-99021 for 4 h [4]. Chir-99021 can activate glycogen synthase in cells. The concentrations of CHIR-99021 causing half-maximal glycogen synthase stimulation (EC50) were 76 nmol/l for CHO-IR cells. A single oral dose of CHIR 99021 (30mg/kg) rapidly lowered plasma glucose in ZDF rats[8]. In combination with different small molecules, CHIR-99021 can facilitate cardiomyocyte differentiation from human embryonic stem cells and iPS cells[10][9], reprogramming, like generation of functional astrocytes from mammalian fibroblasts[10] and maintaining undifferentiated mouse ES cells in the absence of LIF[11].
作用机制 CHIR 99021 can inhibit GSK3 by competing for their ATP-binding sites.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human 769-P cell Growth inhibition assay Inhibition of human 769-P cell growth in a cell viability assay, IC50=584.99 nM. SANGER
human A172 cell Growth inhibition assay Inhibition of human A172 cell growth in a cell viability assay, IC50=3.75498 μM. SANGER
human A498 cell Growth inhibition assay Inhibition of human A498 cell growth in a cell viability assay, IC50=1.3 μM. SANGER
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.15mL

0.43mL

0.21mL

10.74mL

2.15mL

1.07mL

21.49mL

4.30mL

2.15mL
参考文献

[1]Martinez A, Castro A, et al. Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation. Med Res Rev. 2002 Jul;22(4):373-84.

[2]Bennett CN, Ross SE, et al. Regulation of Wnt signaling during adipogenesis. J Biol Chem. 2002 Aug 23;277(34):30998-1004. Epub 2002 Jun 7.

[3]Ring DB, Johnson KW, et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.

[4]Lian X, Zhang J, et al. Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions. Nat Protoc. 2013 Jan;8(1):162-75.

[5]Tian E, Sun G, et al. Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes. Cell Rep. 2016 Jul 19;16(3):781-92.

[6]Ying QL, Wray J, et al. The ground state of embryonic stem cell self-renewal. Nature. 2008 May 22;453(7194):519-23.

[7]CHIR99021 attenuates mood-related behaviors in lithium responsive and non responsive

[8]Ring DB, Johnson KW, Henriksen EJ, Nuss JM, Goff D, Kinnick TR, Ma ST, Reeder JW, Samuels I, Slabiak T, Wagman AS, Hammond ME, Harrison SD. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95. doi: 10.2337/diabetes.52.3.588. PMID: 12606497.

[9]Lian X, Zhang J, Azarin SM, Zhu K, Hazeltine LB, Bao X, Hsiao C, Kamp TJ, Palecek SP. Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions. Nat Protoc. 2013 Jan;8(1):162-75. doi: 10.1038/nprot.2012.150. Epub 2012 Dec 20. PMID: 23257984; PMCID: PMC3612968.

[10]Lian X, Hsiao C, Wilson G, Zhu K, Hazeltine LB, Azarin SM, Raval KK, Zhang J, Kamp TJ, Palecek SP. Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):E1848-57. doi: 10.1073/pnas.1200250109. Epub 2012 May 29. PMID: 22645348; PMCID: PMC3390875.

[11]Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A. The ground state of embryonic stem cell self-renewal. Nature. 2008 May 22;453(7194):519-23. doi: 10.1038/nature06968. PMID: 18497825; PMCID: PMC5328678.