aladdin 阿拉丁 C407831 CHIR-99021（CT99021）盐酸 1797989-42-4 10mM in DMSO

中文名：CHIR-99021（CT99021）盐酸

英文名：CHIR-99021 (CT99021) HCl

纯度：≥97%

货号：C412812

Cas号：1797989-42-4

存储温度：避光,-20°C储存

运输条件：超低温运输

产品介绍：

Information

CHIR-99021 (CT99021) HCl is hydrochloride of CHIR-99021, which is aGSK-3α/βinhibitor withIC50of 10 nM/6.7 nM; CHIR-99021 shows greater than 500-fold selectivity for GSK-3 versus its closest homologs Cdc2 and ERK2. CHIR-99021 is a potent pharmacological activators of theWnt/beta-cateninsignaling pathway. CHIR-99021 significantly rescues light-inducedautophagyand augments GR, RORα and autophagy-related proteins.

Targets

GSK-3β (Cell-free assay); GSK-3α (Cell-free assay) 6.7 nM; 10 nM

In vitro

CHIR-99021 shows greater than 500-fold selectivity for GSK-3 versus its closest homologs CDC2 and ERK2, as well as other protein kinases. Furthermore, CHIR-99021 shows only weak binding to a panel of 22 pharmacologically relevant receptors and little inhibitory activity against a panel of 23 nonkinase enzymes. CHIR-99021 induces the activation of glycogen synthase (GS) in insulin receptor-expressing CHO-IR cells with EC50 of 0.763 μM. In addition to simulating the actions of insulin, inhibition of GSK-3 by CHIR-99021 (3 μM) increases free cytosolic β-catenin by 1.9-fold, mimicking the canonical Wnt signaling pathway in 3T3-L1 preadipocytes. During any of the first 3 days of differentiation, CHIR-99021 treatment inhibits the preadipocyte differentiation with IC50 of 0.3 μM by blocking induction of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ). Unlike lithium chloride and AR-A014418, CHIR-99021 treatment does not reduce the viability of INS-1E cells even at high concentrations. Instead, CHIR-99021 robustly increases the rate of proliferation of INS-1E cells in a dose-dependent manner, and significantly inhibits INS-E cell death induced by high glucose and high palmitate in a concentration-dependent manner. CHIR-99021 promotes primary beta cell replication in isolated rat islets at concentrations as low as 1 μM, with 2-3 fold increase of cell replication at 5 μM of CHIR-99021 treatment.

In vivo

Oral administration of CHIR-99021 at 30 mg/kg enhances glucose metabolism in a rodent model of type 2 diabetes, with a maximal plasma glucose reduction of nearly 150 mg/dl 3-4 hours after administration, while plasma insulin remains at or below control levels. Oral administration of CHIR-99021 at 16 or 48 mg/kg 1 hour before oral glucose challenges in ZDF rats significantly improves glucose tolerance with 14% and 33% reduction in plasma glucose at 16 mg/kg and 48 mg/kg, respectively, and the higher dose of CHIR-99021 also reduces hyperglycemia before the oral glucose challenge. Administration of CHIR-99021 significantly augments hematopoietic repopulation in recipient mice transplanted with mouse or human hematopoietic stem cells (HSCs), suggesting that GSK-3 is a specific modulator of HSC activity.

Cell Research(from reference)

Cell lines：INS-1E 

Concentrations：Dissolved in DMSO, final concentrations ~ 20 μM 

Incubation Time：1, or 4 days 

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