本文（Discovery of New Azaindole Metallo-Deubiquitinase CSN5 Inhibitors ） 原载 J. Med. Chem ， 由 四川大学李国菠教授 等科研人员创作，系四川智慧社会智能治理重点实验室智慧法治研究所 的 系列学术成果。 本网站 后续 将 持续分享实验室 的 系列学术成果，欢迎大家阅读 。
Abstract: CSN5 is responsible for the deneddylation of cullin-RING E3 ubiquitin ligases and is closely linked to the development of various cancers. We previously developed a noncatalytic activity assay platform using novel fluorescent probes derived from azaindole inhibitors, which also highlighted the potential for further structural optimization of azaindoles. Herein, we report a series of new 4-NH-substituted azaindole derivatives, some of which showed nanomolar activity against the CSN5 subunit. Cellular assays revealed that the new azaindoles increase the cullin 1 neddylation in cancer cells. Importantly, they exhibit synergistic anticancer effects in combination with poly(ADP-ribose) polymerase inhibitors through increasing DNA damage. This work presents a new lead compound and a potential combination strategy for drug discovery targeting CSN5.
Lei, P.; Yan, Y.-H.; Jiang, Y.; Wang, Y.; Xiong, R.; Deng, J.; Zhang, H.; Yang, Z.; Zhang, W.; Wu, J.-W.; Liu, W.; Lei, H.; Li, G.-B.; Yang, L. Discovery of New Azaindole Metallo-Deubiquitinase CSN5 Inhibitors. J. Med. Chem. 2025, 68, 6748-6765. （论文下载）
