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Updated: Nov 7, 2025
Author Spotlight: Purifying High-Quality Tubulin to Study Protein Dynamics and Therapeutic Applications
Published on: October 11, 2024
Tubulin Inhibitors: A Chemoinformatic Analysis Using Cell-Based Data
Edgar López-López1,2, Carlos M Cerda-García-Rojas1, José L Medina-Franco2
1Departamento de Química y Programa de Posgrado en Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, Mexico City 07000, Mexico.
Abstract:
Inhibiting the tubulin-microtubules (Tub-Mts) system is a classic and rational approach for treating different types of cancers. A large amount of data on inhibitors in the clinic supports Tub-Mts as a validated target. However, most of the inhibitors reported thus far have been developed around common chemical scaffolds covering a narrow region of the chemical space with limited innovation. This manuscript aims to discuss the first activity landscape and scaffold content analysis of an assembled and curated cell-based database of 851 Tub-Mts inhibitors with reported activity against five cancer cell lines and the Tub-Mts system. The structure-bioactivity relationships of the Tub-Mts system inhibitors were further explored using constellations plots. This recently developed methodology enables the rapid but quantitative assessment of analog series enriched with active compounds. The constellations plots identified promising analog series with high average biological activity that could be the starting points of new and more potent Tub-Mts inhibitors.
Insights
This study analyzes 851 tubulin-microtubules (Tub-Mts) inhibitors, revealing a need for novel chemical scaffolds. Constellation plots identified promising new Tub-Mts inhibitor series for cancer treatment.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Drug Discovery
Background:
- Targeting the tubulin-microtubules (Tub-Mts) system is a validated strategy for cancer therapy.
- Existing Tub-Mts inhibitors often rely on limited chemical scaffolds, hindering innovation.
Purpose of the Study:
- To perform the first activity landscape and scaffold content analysis of Tub-Mts inhibitors.
- To explore structure-bioactivity relationships using novel methodologies.
Main Methods:
- Assembled and curated a cell-based database of 851 Tub-Mts inhibitors.
- Utilized constellation plots for quantitative assessment of analog series.
- Analyzed inhibitor activity against five cancer cell lines and the Tub-Mts system.
Main Results:
- Characterized the activity landscape and scaffold diversity of Tub-Mts inhibitors.
- Identified promising analog series with high average biological activity.
- Constellation plots enabled rapid assessment of structure-bioactivity relationships.
Conclusions:
- The study highlights limitations in current Tub-Mts inhibitor scaffolds.
- Identified novel starting points for developing more potent anti-cancer agents.
- The methodology provides a rapid quantitative assessment for drug discovery.
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