FDA Approved Niraparib-based Virtual Screening and Molecular Docking Studies to Discover Novel 6NRF Protein Modulator for Ovarian Cancer

Abstract

The abstract summarizes the findings of a comprehensive analysis of chemical compounds, focusing on their potential therapeutic relevance in ovarian cancer treatment. Utilizing data from the ChEMBL database, pharmacophore-based screening identified compounds with promising activity against ovarian cancer, with notable catching scores ranging from 0.556 to 1.000. Crystallographic refinement metrics highlighted improvements in structural accuracy and quality following PDB-REDO refinement, with reductions in R and R-free values and significant enhancements in bond length RMS Z-scores. Molecular docking studies revealed predicted binding affinities ranging from -9.6 to -8.4, indicating strong interactions with target proteins. ADME analysis of niraparib, a lead compound, demonstrated favorable physicochemical properties and pharmacokinetic profiles, with Lipinski, Ghose, Veber, and Egan’s rules for drug-likeness and bioavailability met. Toxicity prediction models identified potential organ toxicity endpoints, with neurotoxicity, respiratory toxicity, and immunotoxicity showing active involvement. These findings underscore the complexity of structure-activity relationships and the importance of predictive models in guiding drug discovery efforts and ensuring safety profiles. Overall, this study provides valuable insights into the landscape of PARP inhibitors and their potential in advancing personalized medicine approaches for ovarian cancer therapy.