GSK-3β inhibitor 2

1702428-31-6

318.35

DMSO : 5 mg/mL (15.71 mM; Need ultrasonic)

Stem Cell/Wnt; PI3K/Akt/mTOR

GSK-3beta inhibitor 2 (Compound 3) is a potent, selective and orally active GSK-3beta inhibitor with an IC₅₀ of 1.1 nM. GSK-3beta inhibitor 2 can cross the blood-brain barrier. GSK-3beta inhibitor 2 has the potential for Alzheimer's disease^[1]. In Vitro: The pyridine carboxamide of GSK-3beta 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-3beta inhibitor 2 does not allow its unambiguous placement in the model, but a small molecule crystal structure of GSK-3beta 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-3beta inhibitor 2^[1]. In Vivo: 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-3beta 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-3beta inhibitor 2 shows only modest brain exposure (B/P = 0.26) as determined as a single time point^[1].