Laduviglusib monohydrochloride

产品说明书

Print
Chemical Structure| 1797989-42-4 同义名 : CT99021 monohydrochloride; CHIR-99021 Monohydrochloride; CT99021 HCl; Laduviglusib HCl
CAS号 : 1797989-42-4
货号 : A219562
分子式 : C22H19Cl3N8
纯度 : 98%
分子量 : 501.8
MDL号 : MFCD30489757
存储条件：

Pure form Keep in dark place, inert atmosphere, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

5% DMSO+30% PEG 300+water 24 mg/mL suspension

生物活性
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[3]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[3]. In combination with different small molecules, CHIR-99021 can facilitate cardiomyocyte differentiation from human embryonic stem cells and iPS cells[5][4], reprogramming, like generation of functional astrocytes from mammalian fibroblasts[5] and maintaining undifferentiated mouse ES cells in the absence of LIF[6].
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 数据源
22RV1 Growth Inhibition Assay IC50=197.424 μM SANGER
23132-87 Growth Inhibition Assay IC50=93.168 μM SANGER
3T3-L1 3 μM Function Assay 4 h Inhibits preadipocyte differentiation 12055200
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.99mL

0.40mL

0.20mL

9.96mL

1.99mL

1.00mL

19.93mL

3.99mL

1.99mL
参考文献

[1]Mussmann R, Geese M, et al. Inhibition of GSK3 promotes replication and survival of pancreatic beta cells. J Biol Chem. 2007 Apr 20;282(16):12030-7.

[2]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.

[3]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.

[4]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.

[5]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.

[6]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.