Ovarian cancer remains a significant cause of mortality in gynecological malignancies. Despite advancements with PARP inhibitors, resistance mechanisms limit their efficacy. UBE2N, a key regulator of homologous recombination and post-replication DNA repair, emerges as a promising therapeutic target. This study aims to identify novel, allosteric inhibitors of UBE2N to overcome PARP inhibitor resistance and improve outcomes for ovarian cancer patients. Leveraging BioSolveIT's SeeSAR and infiniSee platforms, we will employ a comprehensive structure-based drug design approach to identify novel UBE2N inhibitors. By leveraging structure-based drug design, we will explore the protein's conformational flexibility and identify potential allosteric binding sites for inhibitors. This approach offers the potential to develop compounds that may overcome limitations associated with current therapeutic options. Through virtual screening and lead optimization, we aim to identify novel UBE2N inhibitors
Shafi Ullah intends to achieve the following milestones:
- In-depth analysis of UBE2N and cofactor interactions, followed by virtual screening of diverse ligand databases,
- Optimizing UBE2Ni Using BioSolveIT Computational Tools
- Identification of hit compounds with promising in vitro activity.