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類器官CHIR-99021

簡要描述:類器官CHIR-99021
類器官(Organoids)是指將成體干細胞或多能干細胞在體外三維培養(yǎng)形成的具有一定空間結構的組織類似物。類器官在組織結構、細胞類型、自我更新能力和功能等方面與來源組織高度一致,從而在發(fā)育生物學、疾病造模、精準醫(yī)學、藥物研發(fā)、基因和細胞療法、感染和免疫以及再生醫(yī)學等生物醫(yī)學的多個領域展現(xiàn)出*的優(yōu)勢。

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  • 更新時間:2024-11-06
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類器官CHIR-99021

類器官(Organoids)是指將成體干細胞或多能干細胞在體外三維培養(yǎng)形成的具有一定空間結構的組織類似物。類器官在組織結構、細胞類型、自我更新能力和功能等方面與來源組織高度一致,從而在發(fā)育生物學、疾病造模、精準醫(yī)學、藥物研發(fā)、基因和細胞療法、感染和免疫以及再生醫(yī)學等生物醫(yī)學的多個領域展現(xiàn)出*的優(yōu)勢。

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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].

類器官CHIR-99021

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