Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.26 (GSK)
 6,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tau hyperphosphorylation and memory deficit are characteristic alterations of Alzheimer's disease (AD), and glycogen synthase kinase-3 (GSK-3) plays a crucial role in these AD-like changes. We have reported that activation of GSK-3 through ventricular injection of wortmannin and GF-109203X (WT/GFX, 100 microM each) induces tau hyperphosphorylation and memory impairment of rats [Liu, S.J. et al., 2003. Overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3 kinase and protein kinase C leads to hyperphosphorylation of tau and impairment of spatial memory. J. Neurochem. 87, 1333-1344]. By using this model, we explored in the present study the effects of dehydroevodiamine (DHED), a quinazoline alkaloid isolated from Evodia rutaecarpa Bentham, on the memory retention, tau phosphorylation and the activity of GSK-3. We found that pre-administration of DHED through vena caudalis for 1 week efficiently improved the WT/GFX-induced spatial memory retention impairment of the rats; it also antagonized tau hyperphosphorylation at multiple AD sites and arrested the overactivation of GSK-3 induced by WT/GFX. Our study gave the first in vivo evidence that DHED could suppress the overactivation of GSK-3 and improve tau hyperphosphorylation and spatial memory deficit of the rats, suggesting that this chemical may be served as a candidate for arresting AD-like pathological and behavioral alterations.
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PMID:Dehydroevodiamine attenuates tau hyperphosphorylation and spatial memory deficit induced by activation of glycogen synthase kinase-3 in rats. 1743 40

Continuous efforts in microwave-assisted synthesis and the structure-activity relationships' (SARs) studies of novel modified 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitriles, allowed identification of new amidine and imidate derivatives as potent and dual CDK1/GSK-3 inhibitors. Combination of lead optimization and molecular modeling studies allowed identification of a dual CDK1/GSK-3 inhibitor (compound 13d) with submicromolar values.
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PMID:Novel 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitrile derivatives as dual cyclin-dependent kinase 1 (CDK1)/glycogen synthase kinase-3 (GSK-3) inhibitors: synthesis, biological evaluation and molecular modeling studies. 1798 70

Mps1, also known as TTK, is a mitotic checkpoint protein kinase that has become a promising new target of cancer research. In an effort to improve the lead-likeness of our recent Mps1 purine lead compounds, a scaffold hopping exercise has been undertaken. Structure-based design, principles of conformational restriction, and subsequent scaffold hopping has led to novel pyrrolopyrimidine and quinazoline Mps1 inhibitors. These new single-digit nanomolar leads provide the basis for developing potent, novel Mps1 inhibitors with improved drug-like properties.
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PMID:Novel Mps1 kinase inhibitors: from purine to pyrrolopyrimidine and quinazoline leads. 2418 38