In-silico-based lead optimization of hit compounds targeting mitotic kinesin Eg5 for cancer management.

ABSTRACT: Lead optimization is vital for turning hit compounds into therapeutic drugs. This study builds upon a prior in silico research, where the hit compounds had better binding affinity and stability compared to a reference drug. Using a genetic algorithm, 12,500 analogs of the top compounds from the prior study were generated. Virtual screening was done using a quantitative structure-activity relationship (QSAR) model. Top analogs, selected based on pChembL values below 6.000nM, underwent molecular docking targeting Human Eg5. The top five analogs from this study (Compound 9794, Compound 8592, Compound 9786, Compound 2744, and Compound 3246) demonstrated strong binding energies and interactions with key amino acids (GLU 116, GLU 117, and ARG 119). MMGBSA analysis revealed comparable affinities

SUBMITTER: Bodun DS 

PROVIDER: S-EPMC11703796 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature