Identification of Novel β-Tubulin Inhibitors Using a Combined <i>In Silico</i>/<i>In Vitro</i> Approach.

ABSTRACT: Due to their potential as leads for various therapeutic applications, including as antimitotic and antiparasitic agents, the development of tubulin inhibitors offers promise for drug discovery. In this study, an in silico pharmacophore-based virtual screening approach targeting the colchicine binding site of β-tubulin was employed. Several structure- and ligand-based models for known tubulin inhibitors were generated. Compound databases were virtually screened against the models, and prioritized hits from the SPECS compound library were tested in an in vitro tubulin polymerization inhibition assay for their experimental validation. Out of the 41 SPECS compounds tested, 11 were active tubulin polymerization inhibitors, leading to a prospective true positive hit rate of 26.8%.

SUBMITTER: Horgan MJ 

PROVIDER: S-EPMC10598795 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature