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Updated: Jun 26, 2025
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Natural compound screening predicts novel GSK-3 isoform-specific inhibitors.
Firdos Ahmad1, Anamika Gupta2, Hezlin Marzook2
1Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, 27272, United Arab Emirates; Cardiovascular Research Group, Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Space Medicine Research Group, Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Researchers screened natural compounds for Glycogen synthase kinase-3 (GSK-3) inhibitors. Psoralidin and Rosmarinic acid showed isoform-specific inhibition, offering potential for treating cardiovascular, metabolic, neurological disorders, and cancer.
Area of Science:
- Biochemistry
- Pharmacology
- Natural Products Chemistry
Background:
- Glycogen synthase kinase-3 (GSK-3) is implicated in cardiovascular, metabolic, neurological disorders, and cancer.
- Current synthetic GSK-3 inhibitors lack specificity and may cause adverse effects.
- Isoform-specific inhibition of GSK-3α or GSK-3β could offer cytoprotective benefits.
Purpose of the Study:
- To identify novel, isoform-specific natural compound inhibitors of GSK-3.
- To evaluate the potential of natural compounds as safer alternatives to synthetic GSK-3 inhibitors.
Main Methods:
- Screening of 70 natural compounds using in silico (molecular docking, pharmacokinetics) and biochemical (kinase assay) approaches.
- Identification of potential GSK-3 inhibitors based on binding affinities and IC50 values.
- Isoform-specific activity assessment against GSK-3α and GSK-3β.
Main Results:
- Psoralidin and Rosmarinic acid were identified as potential GSK-3 inhibitors.
- Psoralidin demonstrated higher affinity and inhibitory effect against GSK-3α (IC50 = 2.26 μM) compared to GSK-3β (IC50 = 4.23 μM).
- Rosmarinic acid showed greater potency against GSK-3β (IC50 = 2.24 μM) than GSK-3α (IC50 = 5.14 μM).
Conclusions:
- Psoralidin and Rosmarinic acid are promising natural inhibitors targeting specific GSK-3 isoforms.
- Psoralidin is a potential inhibitor for GSK-3α, while Rosmarinic acid is a potential inhibitor for GSK-3β.
- Further in vitro and preclinical studies are warranted to validate their therapeutic potential for various diseases.
