类器官CHIR-99021

简要描述:类器官CHIR-99021
类器官(Organoids)是指将成体干细胞或多能干细胞在体外三维培养形成的具有一定空间结构的组织类似物。类器官在组织结构、细胞类型、自我更新能力和功能等方面与来源组织高度一致,从而在发育生物学、疾病造模、精准医学、药物研发、基因和细胞疗法、感染和免疫以及再生医学等生物医学的多个领域展现出*的优势。

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  • 更新时间:2023-11-07
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类器官CHIR-99021

类器官(Organoids)是指将成体干细胞或多能干细胞在体外三维培养形成的具有一定空间结构的组织类似物。类器官在组织结构、细胞类型、自我更新能力和功能等方面与来源组织高度一致,从而在发育生物学、疾病造模、精准医学、药物研发、基因和细胞疗法、感染和免疫以及再生医学等生物医学的多个领域展现出*的优势。

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DESCRIPTION

BackgroundCHIR-99021 is a potent and selective GSK-3α/β inhibitor with IC50s of 10 nM and 6.7 nM. Laduviglusib shows >500-fold selectivity for GSK-3 over CDC2, ERK2 and other protein kinases. Laduviglusib is also a potent Wnt/β-catenin signaling pathway activator. Laduviglusib enhances mouse and human embryonic stem cells self-renewal. Laduviglusib induces autophagy[1][2][3].
Alias

Laduviglusib; CT99021

 
M. W t465.34
FormulaC22H18Cl2N8
CAS No252917-06-9
StoragePowder-20°C3 years
4°C2 years                               C22H18Cl2N8
In solvent-80°C6 months         
-20°C1 month
SolubilityDMSO       16.67 mg/mL(35.82 mM)

H2O< 0.1 mg/mL(insoluble)

BIOLOGICAL ALTIVITY
In Vitro  
CHIR-99021 inhibits human GSK-3β with Ki values of 9.8 nM[1]. Laduviglusib is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that Laduviglusib specifically inhibits GSK3β (IC50=~5 nM) and GSK3α (IC50=~10 nM), with little effect on other kinases[4]. In the presence of Laduviglusib the viability of the ES-D3 cells is reduced by 24.7% at 2.5 μM, 56.3% at 5 μM, 61.9% at 7.5 μM and 69.2% at 10 μM Laduviglusib with an IC50 of 4.9 mm[2].
In Vivo
In ZDF rats, a single oral dose of Laduviglusib (16 mg/kg or 48 mg/kg) rapidly lowers plasma glucose, with a maximal reduction of nearly 150 mg/dl 3-4 h after administration[1]. Laduviglusib (2 mg/kg) given once, 4 h before irradiation, significantly improves survival after 14.5 Gy abdominal irradiation (ABI). Laduviglusib treatment significantly blocks crypt apoptosis and accumulation of p-H2AX+ cells, and improves crypt regeneration and villus height. Laduviglusib treatment increases Lgr5+ cell survival by blocking apoptosis, and effectively prevents the reduction of Olfm4, Lgr5 and CD44 as early as 4 h[5].

类器官CHIR-99021

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