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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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In silico identification of prospective p53-MDM2 inhibitors from ASINEX database using a comprehensive molecular
Dushyant D Kotadiya1, Apurva Prajapati1, Dharmesh A Patel1
1Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India.
Scientific Reports
|October 6, 2025
Summary
Researchers identified novel small-molecule inhibitors targeting MDM2 to restore tumor suppressor p53 function in cancer. These compounds show promise for developing new cancer therapies by reactivating the p53-MDM2 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Cancer cells exhibit high evolutionary potential, leading to drug resistance and reduced treatment efficacy.
- The tumor suppressor protein p53 is crucial for cellular regulation but often inactivated in cancers by MDM2 and MDMX.
- Targeting MDM2 with small-molecule inhibitors to reactivate p53 is a key strategy in oncology drug development.
Purpose of the Study:
- To identify high-affinity MDM2 binders through structure-based virtual screening.
- To evaluate potential anticancer drug candidates for the p53-MDM2 pathway.
Main Methods:
- Structure-based virtual screening of 261,120 compounds from the Asinex database.
- Molecular docking, ADMET profiling, and molecular dynamics (MD) simulations using Schrödinger's Maestro platform.
- Density Functional Theory (DFT) computations for electronic properties and stability analysis.
Main Results:
- Identified lead compounds with high binding affinities for MDM2.
- Generated compounds demonstrated favorable pharmacokinetic properties.
- Assessed electronic properties and stability using DFT computations.
Conclusions:
- The identified lead compounds serve as suitable scaffolds for further therapeutic investigation.
- Findings support the development of next-generation inhibitors targeting the p53-MDM2 pathway.
- This study provides a foundation for experimental validation of novel anticancer agents.
