Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Glycogen synthase kinase 3 (GSK-3) has become known for its multifactorial involvement in the pathogenesis of Alzheimer's disease. In this study, a benzothiazole- and benzimidazole set of 1-aryl-3-(4-methoxybenzyl)ureas were synthesised as proposed Cys199-targeted covalent inhibitors of GSK-3β, through the incorporation of an electrophilic warhead onto their ring scaffolds. The nitrile-substituted benzimidazolylurea 2b (IC = 0.086 ± 0.023 µM) and halomethylketone-substituted benzimidazolylurea 9b (IC = 0.13 ± 0.060 µM) displayed high GSK-3β inhibitory activity, in comparison to reference inhibitor AR-A014418 (1, IC = 0.072 ± 0.043) in our assay. The results suggest further investigation of 2b and 9b as potential covalent inhibitors of GSK-3β, since a targeted interaction might provide improved kinase-selectivity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2019.04.049 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Role of GSK-3 Inhibition in Alzheimer's Disease Therapy.
Curr Alzheimer Res
September 2025
Department of Biochemistry, General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia.
A serine/threonine kinase with a wide variety of substrates, Glycogen Synthase Kinase-3 (GSK-3) is widely expressed. GSK-3 is a key player in cell metabolism and signaling, modulating numerous cellular functions and playing significant roles in both healthy and diseased states. The two histopathological features of Alzheimer's disease, the intracellular neurofibrillary tangles composed of hyperphosphorylated tau, and the extracellular senile plaques composed of beta-amyloid, have been linked to GSK-3.
View Article and Find Full Text PDFHeterogeneous nuclear ribonucleoprotein A/B drives gastric cancer and epithelial-mesenchymal transition via the Akt-GSK3β-Wnt pathway.
Mol Pharmacol
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Genomic Medicine, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Gu
Gastric cancer (GC) is a leading cause of cancer-related deaths globally, with metastasis critically impacting prognosis. Splicing factors are key regulators of tumorigenesis, particularly in metastasis. In this exploratory study, we investigated the role and mechanism of heterogeneous nuclear ribonucleoprotein A/B (HNRNPAB) in GC cell invasion and migration.
View Article and Find Full Text PDFIn vitro formation and growth of glycogen: experimental verification of theoretical predictions.
Carbohydr Polym
November 2025
Jiangsu Key Laboratory of Crop Genetics and Physiology, Key Laboratory of Plant Functional Genomics of the Ministry of Education, College of Agriculture, Yangzhou University, Yangzhou 225009, Jiangsu Province, China; Co-Innovation Centre for Modern Production Technology of Grain Crops, Yangzhou Univ
Glycogen is a complex branched glucose polymer that serves as energy reservoir in animals and some bacteria; it has also been synthesized in vitro. It comprises small β particles linked in large aggregates termed α particles. Theory, based on the evolutionary processes which cause these particles to be formed, suggests that if all ingredients for in vitro particle synthesis were added to a suspension of α particles, then these will grow to a steady-state size distribution, after which new particles will be formed.
View Article and Find Full Text PDFDapagliflozin Ameliorates Doxorubicin-Induced Chemobrain and Cognitive Abnormalities in Rats: Modulation of AKT/GSK-3β and Wnt/β-Catenin Pathways.
Neurochem Res
September 2025
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Cognitive impairments are frequently observed in cancer survivors who received chemotherapy based on doxorubicin (DOX), attributable to oxidative stress, neuroinflammation, and the apoptotic effect of DOX. Dapagliflozin (DAPA) has gained significant attention attributable to its powerful anti-inflammatory, antioxidant, and anti-apoptotic characteristics. The present investigation seeks to assess the possible neuroprotective properties of DAPA in alleviating neurodegeneration and cognitive dysfunction caused by DOX.
View Article and Find Full Text PDFApoE4 Upregulates GSK-3β to Aggravate Alzheimer-Like Pathologies and Cognitive Impairment in Type 2 Diabetic Mice.
CNS Neurosci Ther
September 2025
Key Laboratory of Ministry of Education for Neurological Disorders, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: The apolipoprotein E (ApoE) ε4 allele and type 2 diabetes mellitus (T2DM) are independent risk factors for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder in the elderly. The T2DM patients carrying the ApoE ε4 allele exhibit heightened activation of platelet glycogen synthase kinase-3β (GSK-3β), a key downstream kinase in the insulin signaling pathway, along with more severe cognitive deficits. This observation suggests an intrinsic link between ApoE ε4, GSK-3β, and cognitive dysfunction.
View Article and Find Full Text PDF