Pharmacy College, Henan University of Chinese Medicine, 450046 Zhengzhou, PR China.
State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Int J Biol Macromol. 2024 Oct;277(Pt 4):134541. doi: 10.1016/j.ijbiomac.2024.134541. Epub 2024 Aug 5.
DCN1, a critical co-E3 ligase in the neddylation process, mediates the activation of Cullin-RING Ligases (CRLs) by selectively catalyzing cullin neddylation, further regulating the activity of substrate proteins. It has been identified as an important target for human diseases, including cancers, fibrotic diseases, and cardiovascular disorders. This work aims to provide a perspective for the discovery of novel DCN1 inhibitors by the analysis of biological roles, protein structures, structure-activity relationships and design strategy disclosed in recent years. Additionally, we will discuss the current status, challenges and opportunities in hope of offering insights into the development of DCN1 inhibitors for human diseases.
DCN1 是 neddylation 过程中的关键共 E3 连接酶，通过选择性催化 Cullin 连接酶 neddylation，进一步调节底物蛋白的活性，从而介导 Cullin-RING 连接酶（CRLs）的激活。它已被确定为人类疾病的重要靶点，包括癌症、纤维化疾病和心血管疾病。本工作旨在通过分析近年来揭示的生物学作用、蛋白质结构、结构-活性关系和设计策略，为新型 DCN1 抑制剂的发现提供新视角。此外，我们将讨论目前的状况、挑战和机遇，希望为 DCN1 抑制剂在人类疾病中的开发提供新的思路。
