Tideglusib

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Chemical Structure| 865854-05-3 同义名 : NP031112;NP-12
CAS号 : 865854-05-3
货号 : A140220
分子式 : C19H14N2O2S
纯度 : 98%
分子量 : 334.392
MDL号 : MFCD18633296
存储条件：

Pure form Inert atmosphere,2-8°C

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

DMSO: 35 mg/mL(104.67 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+30% PEG300+water 2 mg/mL clear

PO 0.5% CMC-Na 14 mg/mL suspension

生物活性
靶点

  • GSK-3β

    GSK-3β, IC50:60 nM
描述 GSK-3 (Glycogen synthase kinase 3) is a serine/threonine protein kinase, consisting of GSK-3 and subunit, 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/-catenin signaling[2][3]. Tideglusib is a thiadiazolidinedione-derived GSK-3 inhibitor with Ki value of 60nM (calculated by double ATP and inhibitor titrations) and can inhibit GSK-3 with IC50 value of 105nM (measured by enzymatic assays of human recombinant GSK-3)[1]. Tideglusib can increase the level of phosphorylated GSK3-S9, as well as decreased the level of phosphorylated tau, in a dose or time dependent manner in GSC11 cells treated on dose of 0-10uM or in 0-6h[4]. Tideglusib shows neuroprotection against hypoxic-ischemic brain injury in neonatal mice. Intraperitoneal administration of tideglusib (5 mg/kg) 20 min prior to the onset of ischemia can reduce cerebral infarct volume at both 24 h and 7 days after hypoxic-ischemic injury[5]. Several clinical studies on neurological diseases, including two phase 2 studies of Alzheimer's disease, have been completed (see in https://www.clinicaltrials.gov/).
作用机制 Tideglusib is a thiadiazolidinedione-derived non-ATP competitive inhibitor of GSK3.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.99mL

0.60mL

0.30mL

14.95mL

2.99mL

1.50mL

29.91mL

5.98mL

2.99mL
参考文献

[1]Domínguez JM, Fuertes A, et al. Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.

[2]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.

[3]Domoto T, Pyko IV, et al. Glycogen synthase kinase-3β is a pivotal mediator of cancer invasion and resistance to therapy. Cancer Sci. 2016 Oct;107(10):1363-1372.

[4]Zhou A, Lin K, et al. Nuclear GSK3β promotes tumorigenesis by phosphorylating KDM1A and inducing its deubiquitylation by USP22. Nat Cell Biol. 2016 Sep;18(9):954-966.

[5]Wang H, Huang S, et al. Tideglusib, a chemical inhibitor of GSK3β, attenuates hypoxic-ischemic brain injury in neonatal mice. Biochim Biophys Acta. 2016 Oct;1860(10):2076-85.

[6]Khan I, Tantray MA, et al. Natural and synthetic bioactive inhibitors of glycogen synthase kinase. Eur J Med Chem. 2017 Jan 5;125:464-477.

[7]Luna-Medina R, Cortes-Canteli M, et al. NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders. J Neurosci. 2007;27(21):5766-76.

[8]Bharathy N, Svalina MN, et al. Preclinical testing of the glycogen synthase kinase-3β inhibitor tideglusib for rhabdomyosarcoma. Oncotarget. 2017;8(38):62976-62983.