International Journal of Drug Delivery Technology
Volume 15, Issue 3

Targeting Mutant P53 (M133l-V203a-Y220c-N239y-N268d) in Cancer: Drug Repurposing via Structure-Based Virtual Screening 

Ganesh Nigade1, Santosh Tarke2, Vishal More3, Santosh Belhekar4

1Department of Pharmaceutical Chemistry, PDEA’s Seth Govind Raghunath Sable College of Pharmacy, Saswad, Affiliated to Savitribai Phule Pune University, Pune, Maharashtra, India

2Department of Pharmacognosy and Phytochemistry, SBSPM’s B. Pharmacy College, Ambajogai, Affiliated to Dr. BAMU, Ch. Sambhaji Nagar, Maharashtra, India

3Department of Pharmaceutical Chemistry, Amrutvahini Sheti and Shikshan Vikas Sanstha’s Amrutvahini College of Pharmacy, Amrutnagar, PO-Sangamner (S.K.), Tal.- Sangamner, Dist.- Ahilya Nagar, Maharashtra-422608, Affiliated to Savitribai Phule Pune University, Pune, Maharashtra, India

4Department of Pharmacology, Gourishankar Institute of Pharmaceutical Education & Research, Limb, Satara, Affiliated to Dr. Babasaheb Ambedkar Technological University, Lonere, Raigad, Maharashtra, India 

Received: 7th Jun, 2025; Revised: 23rd Jul, 2025; Accepted: 13th Aug, 2025; Available Online: 25th Sep, 2025 

ABSTRACT

The tumor suppressor protein p53 has a mutant form, p53-Y220C, which is structurally destabilized and frequently is associated with enhanced cancer progression. The present study undertook the refinement of the crystal structure of the mutant (PDB ID: 2J1X) using the server PDB-REDO, so that the model would improve its quality by the R-free value from 0.2041 to 0.1791, increasing above the 89% favorite Ramachandran residues to 95%. Structural validation ProSA-Web Z-score of -6.03 indicates reliability of the model according to the analysis of up to number ERRAT Overall Quality Factor 94.72%. Virtual screening of FDA-approved drugs applied Paritaprevir (-9.6 kcal/mol), Eribulin (-9.5), and Dutasteride (-9.3 kcal/mol) as candidates stabilizing mutant cavity. VERIFY 3D analysis confirmed refined model with 93.08% residues scoring ≥0.1. These output states that the optimized p53-Y220C mutant structure is applicable for in silico drug screening paving the way for more experimental validation of repurposed drug candidates.

Keywords: p53-Y220C mutant, structural refinement, virtual screening, molecular docking, drug repurposing, PDB-REDO, ProSA-Web, ERRAT, VERIFY 3D

How to cite this article: Ganesh Nigade, Santosh Tarke, Vishal More, Santosh Belhekar. Targeting Mutant P53 (M133l-V203a-Y220c-N239y-N268d) in Cancer: Drug Repurposing via Structure-Based Virtual Screening. International Journal of Drug Delivery Technology. 2025;15(3):1228-36. doi: 10.25258/ijddt.15.3.43

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