• Uma Kumari
• Saksham Bhatia

Abstract: Oral cancer continues to be a critical health issue worldwide, requiring the development of more effective and targeted treatments. This research utilizes Next-Generation Sequencing (NGS) technologies to uncover potential therapeutic targets specific to oral cancer. Focusing on the protein structure with PDB ID: 6V3W, our analysis identifies Human Poly (ADP-Ribose) Polymerase 12 (PARP12) as a promising candidate due to its involvement in immune response modulation and DNA repair, and its structural association with the PD-L1 pathway. A combination of bioinformatics tools and computational biology techniques was applied to validate the target and evaluate potential drug candidates. Structural validation of 6V3W using ERRAT and PDBsum confirmed the reliability of the protein model. Sequence conservation was assessed through multiple alignment and phylogenetic analysis in Jalview, while PyMOL provided three-dimensional visualization of key residues and active sites. Molecular docking, performed with CB-Dock, identified strong interactions between PARP12 and the inhibitor RBN-2397, particularly involving residues such as GLU542 and TYR546. Toxicity assessment using ProTox-III suggested a favorable safety profile for the compound. Additional insights were gained from domain analysis using PROSITE and InterProScan, confirming characteristic PARP features. Pathway and interaction mapping through KEGG and STRING databases revealed the role of PARP12 in essential cellular mechanisms, including immune regulation and DNA maintenance. Custom Python scripts developed using Biopython supported sequence annotation, domain identification, and streamlined data analysis. This study demonstrates the potential of PARP12 as a therapeutic target in oral cancer and presents a robust computational framework for identifying and validating drug candidates with low toxicity, contributing to the advancement of precision medicine in oncology.

Oral cancer; Next-Generation Sequencing (NGS); Target identification; Drug inhibitors; Toxicity validation; Molecular docking; Precision oncology; Oncogenic pathways; Structure-based drug design

"NGS, TARGET IDENTIFICATION AND TOXICITY VALIDATION OF NOVEL DRUG INHIBITORS FOR ORAL CANCER", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.12, Issue 6, page no.b193-b208, June-2025, Available :http://www.jetir.org/papers/JETIR2506125.pdf

"NGS, TARGET IDENTIFICATION AND TOXICITY VALIDATION OF NOVEL DRUG INHIBITORS FOR ORAL CANCER", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.12, Issue 6, page no. ppb193-b208, June-2025, Available at : http://www.jetir.org/papers/JETIR2506125.pdf