Related Experiment Video
Updated: Jul 2, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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.
Abstract:
Cancer cells have a higher evolutionary potential than normal cells, which commonly leads to medication resistance and a decrease in the efficacy of existing cancer treatments. As a result, discovering new therapeutic drugs is an important priority in the field of oncology. The tumor suppressor protein p53, regulates many cellular activities but is frequently rendered inactive in malignancies due to aberrant overproduction of MDM2 and MDMX. As a result, the method of targeting MDM2 with small-molecule inhibitors to reactivate p53 signalling has gained popularity as a promising approach for anticancer drug development. In this study, we performed a comprehensive structure-based virtual screening of 261,120 compounds from the Asinex database, along with molecular docking, ADMET profiling, and molecular dynamics (MD) simulations using Schrödinger's Maestro platform, to identify high-affinity MDM2 binders. electronic properties and stability characteristics have been assessed using Density Functional Theory (DFT) computations. The generated lead compounds had favourable pharmacokinetic features and high binding affinities for MDM2, making them suitable scaffolds for further therapeutic study. Overall, our findings lay the groundwork for experimental validation and drive the hunt for next-generation inhibitors of the p53-MDM2 pathway in cancer therapy.
Insights
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.
