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Updated: Oct 12, 2025

Author Spotlight: Purifying High-Quality Tubulin to Study Protein Dynamics and Therapeutic Applications
Published on: October 11, 2024
Discovery of novel tubulin inhibitors targeting the colchicine binding site via virtual screening, structural
Wei Liu1, Hairui Jia2, Minghao Guan3
1Department of Medicinal Chemistry and Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi Province, China; Faculty of Pharmacy, School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an, Shaanxi Province, China.
Abstract:
The colchicine binding site of tubulin is a promising target for discovering novel antitumor agents which exert the antiangiogenic effect and are not susceptible to multidrug resistance. For identifying novel tubulin inhibitors, structure-based virtual screening was applied to identify hit 9 which displayed moderate tubulin polymerization inhibition and broad-spectrum in vitro antitumor activity. Structural optimization was performed, and biological assay revealed analog E27 displayed the best antitumor activity with IC50 values ranging from 7.81 μM to 10.36 μM, and improved tubulin polymerization inhibitory activity (IC50 = 16.1 μM). It significantly inhibited cancer cell migration and invasion, induced cell apoptosis and arrested the cell cycle at G2/M phase. Moreover, the apoptotic effect of E27 is related to the increased ROS level, the decrease of MMP, and the abnormal expression of apoptosis-related proteins. Taken together, these results suggested E27 was a promising lead compound for discovering novel tubulin-targeted antitumor agents.
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