GSK-3β inhibitor 2 

GSK-3β inhibitor 2 (Compound 3) is a potent, selective and orally active GSK-3β inhibitor with an IC₅₀ of 1.1 nM. GSK-3β inhibitor 2 can cross the blood-brain barrier. GSK-3β inhibitor 2 has the potential for Alzheimer's disease^[1].

The pyridine carboxamide of GSK-3β inhibitor 2 (Compound 3) makes hydrogen bonds with the hinge V135 backbone amide, and the carbonyl oxygen of the thiazolyl primary amide formed a critical hydrogen bond with K85. The quality of the electron density for the methyl group of the methoxy moiety in GSK-3β inhibitor 2 does not allow its unambiguous placement in the model, but a small molecule crystal structure of GSK-3β inhibitor 2 determined by single crystal X-ray diffraction method confirmed the intramolecular hydrogen bonding between the methoxy -O- and the amide N-H in GSK-3β inhibitor 2^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

The elevation of hyperphosphorylated Tau (pTau) is mimicked in LaFerla 3xTg-C57BL6 mice, and accordingly, these mice are used as an in vivo model of Alzheimer’s disease. GSK-3β inhibitor 2 (Compound 3) shows a significant reduction in pTau396 when administered orally at 30 mg/kg as a nanosuspension to LaFerla 3xTg-C57BL6 male mice. GSK-3β inhibitor 2 shows only modest brain exposure (B/P = 0.26) as determined as a single time point^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

318.35

C₁₄H₁₄N₄O₃S

1702428-31-6

Solid

Light yellow to yellow

O=C(C1=C(OC)N=C(C2=CC(NC(C3CC3)=O)=NC=C2)S1)N

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Sivaprakasam P, et al. Discovery of new acylaminopyridines as GSK-3 inhibitors by a structure guided in-depth exploration of chemical space around a pyrrolopyridinone core. Bioorg Med Chem Lett. 2015 May 1;25(9):1856-63.  [Content Brief]