A comprehensive review on DCN1 protein, inhibitors and their therapeutic applications.

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.