1. PI3K/Akt/mTOR
    Stem Cell/Wnt
  2. GSK-3

Tideglusib (Synonyms: NP-12; NP031112)

Cat. No.: HY-14872 Purity: 99.81%
Handling Instructions

Tideglusib is an irreversible GSK-3 inhibitor with IC50 of 5 nM and 60 nM for GSK-3βWT (1 h preincubation) and GSK-3βC199A (1 h preincubation), respectively.

For research use only. We do not sell to patients.
Tideglusib Chemical Structure

Tideglusib Chemical Structure

CAS No. : 865854-05-3

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 110 In-stock
10 mg USD 100 In-stock
50 mg USD 168 In-stock
100 mg USD 319 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Tideglusib is an irreversible GSK-3 inhibitor with IC50 of 5 nM and 60 nM for GSK-3βWT (1 h preincubation) and GSK-3βC199A (1 h preincubation), respectively.

IC50 & Target

IC50: 5 nM (GSK-3βWT), 60 nM (GSK-3βC199A)[1]

In Vitro

Tideglusib (NP12) is a small heterocyclic thiadiazolidinone (TDZD) derivative, which is an ATP-non competitive inhibitor of GSK-3β with an IC50 value in the micromolar range[2]. Incubation of both astrocyte and microglial cultures with Tideglusib (NP031112) completely abrogates the induction of TNF-α and COX-2 expression after glutamate treatment. These effects of NP031112 are not caused by a loss of cell viability, because the 24 h exposure of astrocyte and microglial cells to this TDZD does not modify cell viability[3].

In Vivo

Tideglusib (NP12) treatment correlates with an increase of 46% as an average in the inhibitory phosphorylation of GSK-3β at Ser-9 in the brains of APPsw-tauvlw mice, and the levels of the inactive from of the enzyme in NP12 treated mice are comparable to those found in wild-type littermate controls (p=0.893) (n=6-8 for each treatment). NP12 treatment results in significantly decreased phosphorylation at the putative GSK-3β-directed sites Ser-202 (CP13) and Ser-396/404 (PHF-1) in 15-month-old mice by more than 60% (p=0.023 and p=0.024, respectively)[2]. Injection of Tideglusib (NP031112) (50 mg/kg) into the rat hippocampus dramatically reduces kainic acid-induced inflammation, as measured by edema formation using T2-weighted magnetic resonance imaging and glial activation and has a neuroprotective effect in the damaged areas of the hippocampus[3].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.9905 mL 14.9526 mL 29.9052 mL
5 mM 0.5981 mL 2.9905 mL 5.9810 mL
10 mM 0.2991 mL 1.4953 mL 2.9905 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[1]

[35S]Tideglusib (207 Bq/nmol) at 55 μM is incubated with 5 μM GSK-3β for 1 h at 25°C in 315 μL of 50 mM Tris-HCl, pH 7.5, containing 150 mM NaCl and 0.1 mM EGTA. The incubation is extended for another 30 min after having added 35 μL of the same buffer with or without 100 mM DTE. Samples are then processed in three different ways. First, an aliquot of 125 μL of each sample is mixed with 375 μL of 8 M GdnHCl in H2O and heated at 80°C for 5 min. A second aliquot of 125 μL is diluted up to 500 μL with H2O and left at room temperature for 5 min. In both cases, the free drug is removed afterwards by gel filtration through Sephadex G-25, and the amount of bound drug is determined by liquid scintillation counting on a 1450-MicroBeta TriLux counter. Finally, a third 40 μL aliquot of each original sample is mixed with 10 μL of denaturing electrophoresis sample buffer without reducing agents, and 35 μL of this mixture is loaded onto a 10% polyacrylamide gel and subjected to SDS-PAGE (again in the absence of reducing agents except for the DTE already included in the corresponding sample), followed by fluorography of the dried gel[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2][3]

Tideglusib (NP12) is reconstituted in 26% peg400 (Polyethylene Glycol 400), 15% Chremophor EL and water (Mice)[2].

Mice[2]
Groups of APPsw-tauvlw mice are administered Tideglusib (n=10-11 for each age) or vehicle (n=10-11 for each age) starting at 9 months and 12 months of age during consecutive 3 months and used for subsequent clinicopathological analyses. Tideglusib is administered at a daily dose of 200 mg/kg. Groups of age and gender-matched wild-type littermate controls (n=10 for each age) receive vehicle alone on a similar timetable schedule. Rats[3]
Adult male Wistar rats (8-12 weeks old) are used in this study. Rats (n≥5 per group) are anesthetized by intraperitoneal injection of ketamine (60 mg/kg) and Domtor (5 μg/kg) and placed into a stereotaxic apparatus. KA (1 μg in 2.5 μL PBS) alone or in combination with Tideglusib (2 ng in 2.5 μL PBS) is injected into the hippocampus. Control animals of the same age are injected with vehicle. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

334.39

Formula

C₁₉H₁₄N₂O₂S

CAS No.

865854-05-3

SMILES

O=C(N(SC1=O)C2=C3C=CC=CC3=CC=C2)N1CC4=CC=CC=C4

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 12.5 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.81%

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number *

 

Organization name *

Country *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
Tideglusib
Cat. No.:
HY-14872
Quantity: