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Updated: Aug 18, 2025
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Integrated virtual screening and MD simulation study to discover potential inhibitors of Lyn-kinase: targeting cancer
Md Imtaiyaz Hassan1, Darakshan Anjum2, Taj Mohammad1
1Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
Abstract:
Tyrosine-protein kinase Lyn (LynK) has emerged as one of the most attractive therapeutic targets for cancer and diabetes. In this study, we used a multistep virtual screening process of natural compounds to discover potential inhibitors of LynK from the IMPPAT database. The primary filters were based on Lipinski rules, ADMET properties, and PAINS patterns. Then, binding affinities and interaction analyses were carried out for the high-affinity selectivity of the compounds towards LynK. Eventually, two natural compounds, Glabrene and Lactupicrin, were identified with high affinity and specificity for the LynK-binding pocket. Both compounds exhibited drug-like properties, as predicted by ADMET analysis and physicochemical parameters. The molecular dynamics (MD) simulation study revealed that these compounds bind to the ATP-binding pocket of LynK and interact with functionally significant residues with stability without inducing any significant structural changes to the protein. Ultimately, the identified compounds may be regarded as promising LynK inhibitors and can be used as lead molecules in the drug development against LynK-related diseases.Communicated by Ramaswamy H. Sarma.
Insights
Researchers identified Glabrene and Lactupicrin as potential inhibitors of Tyrosine-protein kinase Lyn (LynK), a target for cancer and diabetes. These natural compounds show high affinity and specificity for LynK, offering promising leads for drug development.
Area of Science:
- Biochemistry
- Pharmacology
- Computational Chemistry
Background:
- Tyrosine-protein kinase Lyn (LynK) is a significant therapeutic target for diseases like cancer and diabetes.
- Identifying novel LynK inhibitors is crucial for developing effective treatments.
Purpose of the Study:
- To discover natural compounds with high affinity and specificity for LynK using virtual screening.
- To evaluate the drug-like properties and binding stability of potential LynK inhibitors.
Main Methods:
- Multistep virtual screening of natural compounds from the IMPPAT database.
- Application of Lipinski rules, ADMET, and PAINS filters for initial compound selection.
- Binding affinity, interaction analysis, and molecular dynamics (MD) simulations to assess compound-protein interactions.
Main Results:
- Glabrene and Lactupicrin were identified as high-affinity and specific inhibitors of LynK.
- Both compounds demonstrated favorable drug-like properties and physicochemical parameters.
- MD simulations confirmed stable binding within the LynK ATP-binding pocket, interacting with key residues without causing structural changes.
Conclusions:
- Glabrene and Lactupicrin are promising natural inhibitors of LynK.
- These compounds can serve as lead molecules for developing drugs against LynK-related diseases.
