GSK-3β inhibitor 2 (Compound 3) 是一种有效，选择性和口服活性的 GSK-3β 抑制剂，IC50 为 1.1 nM。GSK-3β inhibitor 2 可以穿越血脑屏障。GSK-3β inhibitor 2 有用于阿尔茨海默氏病的潜力。
货号:ajcx32920
CAS:1702428-31-6
分子式:C14H14N4O3S
分子量：318.35
溶解度:DMSO : 5 mg/mL (15.71 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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].

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].

[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.