Tubulin Inhibitors: A Chemoinformatic Analysis Using Cell-Based Data

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 9; p. 2483
• Main Authors: López-López, Edgar, Cerda-García-Rojas, Carlos M, Medina-Franco, José L
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.04.2021; MDPI
• Subjects: activity landscape; analog series; Binding sites; Biological activity; Cancer; Cell cycle; Cell Line, Tumor; cell-based assays; chemical space; Cheminformatics; chemoinformatics; Constellations; Content analysis; Datasets; drug discovery; Humans; Hydrogen bonds; Inhibitors; Microtubules; Neoplasms - drug therapy; Neoplasms - genetics; Polymerization; Quantitative analysis; Scaffolds; Tubs; Tubulin; Tubulin - chemistry; Tubulin - drug effects; Tubulin - genetics; Tubulin Modulators - chemistry; Tubulin Modulators - pharmacology; Tumor cell lines; constellation plots; structure–property relationships; drug discovery; scaffold; activity landscape; chemoinformatics; cell-based assays; analog series; chemical space; microtubules
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26092483

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.