López-López Edgar, Cerda-García-Rojas Carlos M, Medina-Franco José L
Departamento 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.
DIFACQUIM Research Group, Department of Pharmacy, School of Chemistry, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Molecules. 2021 Apr 24;26(9):2483. 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.
抑制微管蛋白-微管（Tub-Mts）系统是治疗不同类型癌症的经典且合理的方法。临床上大量关于抑制剂的数据支持Tub-Mts作为一个经过验证的靶点。然而，迄今为止报道的大多数抑制剂都是围绕常见化学骨架开发的，这些骨架覆盖的化学空间区域狭窄，创新有限。本手稿旨在讨论一个经过组装和整理的基于细胞的数据库的首次活性景观和支架内容分析，该数据库包含851种Tub-Mts抑制剂，这些抑制剂对五种癌细胞系和Tub-Mts系统具有报道的活性。使用星座图进一步探索了Tub-Mts系统抑制剂的结构-生物活性关系。这种最近开发的方法能够快速但定量地评估富含活性化合物的类似物系列。星座图确定了具有高平均生物活性的有前景的类似物系列，这些系列可能是新型更强效Tub-Mts抑制剂的起点。
