GSK-3β inhibitor 2

Research use only, not for human use.

GSK-3β inhibitor 2 is a BBB-crossing and selective inhibitor of GSK-3β (IC50 = 1.1 nM). GSK-3β inhibitor 2 can be used in studies about Alzheimer's disease.

GSK-3β inhibitor 2 is a BBB-crossing and selective inhibitor of GSK-3β (IC50 = 1.1 nM). GSK-3β inhibitor 2 can be used in studies about Alzheimer's disease.(In Vitro):The pyridine carboxamide of GSK-3β inhibitor 2 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 intramolecular hydrogen bonding between the methoxy -O- and the amide N-H in GSK-3β inhibitor 2 is confirmed by single crystal X-ray diffraction method.(In Vivo):In LaFerla 3xTg-C57BL6 mice with Alzheimer’s disease, GSK-3β inhibitor 2 (30 mg/kg; oral) significantly reduces hyperphosphorylated Tau396. GSK-3β inhibitor 2 shows only modest brain exposure (B/P = 0.26), determined as a single time point.

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.

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.

5-Thiazolecarboxamide,2-[2-[(cyclopropylcarbonyl)amino]-4-pyridinyl]-4-methoxy- | GSK 3β inhibitor 2

PI3K/Akt/mTOR signaling

GSK-3

D3

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1702428-31-6

318.35

C14H14N4O3S

>98% (HPLC)

In Vitro:?DMSO : 5 mg/mL (15.71 mM)

COc1nc(sc1C(N)=O)-c1ccnc(NC(=O)C2CC2)c1

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(-20℃)

With Ice Pack

≥ 2 years