product name Tideglusib
Description: Tideglusib is an irreversible, non ATP-competitive GSK-3β inhibitor with IC50 of 60 nM in a cell-free assay; fails to inhibit kinases with a Cys homologous to Cys-199 located in the active site. Tideglusib is currently undergoing phase II clinical trials for Alzheimer disease and progressive supranuclear palsy. In vitro studies showed that after the unbound Tideglusib was removed from the reaction medium, the enzyme function could not be recovered. In addition, the dissociation rate constant of the reaction was as low as nearly zero.
References: J Biol Chem. 2012 Jan 6;287(2):893-904; J Neurosci. 2007 May 23;27(21):5766-76.
334.39
Formula
C19H14N2O2S
CAS No.
865854-05-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 66 mg/mL (197.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
4% DMSO+corn oil: 2.5 mg/mL
Synonyms
NP031112, NP-12
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19423840
| In Vitro |
In vitro activity: Tideglusib irreversibly inhibits GSK-3, reduces tau phosphorylation, and prevents apoptotic death in human neuroblastoma cells and murineprimary neurons. Tideglusib (2.5 μM) inhibits glutamate-induced glial activation as evidenced by decreased TNF-α and COX-2 expression in rat primary astrocyte or microglial cultures. Tideglusib (2.5 μM) also exerts a potent neuroprotective effect on cortical neurons from glutamate-induced excitotoxicity as evidenced by significant reduction in the number of Annexin-V-positive cells in rat primary astrocyte or microglial cultures. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Tideglusib (50 mg/kg) injected into the adult male Wistar rats hippocampus dramatically reduces kainic acid-induced inflammation and has a neuroprotective effect in the damaged areas of the hippocampus. Tideglusib (200 mg/kg, oral) results in lower levels of tau phosphorylation, decreased amyloid deposition and plaque-associated astrocytic proliferation, protection of neurons in the entorhinal cortex and CA1 hippocampal subfield against cell death, and prevention of memory deficits in APP/tau double transgenic mice. |
| Animal model | Transgenic APPsw-tauvlw mice overexpressing human mutant APP and a triple human tau mutation. |
| Formulation & Dosage | Formulated in 26% peg400 (Polyethylene Glycol 400), 15% Chremophor EL and water; 200 mg/kg; Oral gavage |
| References | J Biol Chem. 2012 Jan 6;287(2):893-904; J Neurosci. 2007 May 23;27(21):5766-76. |
