蛋白质neddylation是一种翻译后修饰，其最受认可的底物是cullin家族蛋白，它是Cullin-RING连接酶（CRL）的核心成分。鉴于大多数 neddylation 途径蛋白在不同的癌症和纤维化疾病中过度激活，靶向 neddylation 成为治疗这些疾病的新兴方法。迄今为止，已有多种neddylation抑制剂被开发出来，其中MLN4924已进入I/II/III期临床试验，用于治疗癌症，如急性髓系白血病、黑色素瘤、淋巴瘤和实体瘤。在这里，我们系统地描述了neddylation中关键酶的结构和生物学功能，重点介绍了neddylation抑制剂开发中的药物化学进展，并提出了针对neddylation治疗癌症和纤维化疾病的观点。©作者。

Protein neddylation is a post-translational modification, and its best recognized substrates are cullin family proteins, which are the core component of Cullin-RING ligases (CRLs). Given that most neddylation pathway proteins are overactivated in different cancers and fibrotic diseases, targeting neddylation becomes an emerging approach for the treatment of these diseases. To date, numerous neddylation inhibitors have been developed, of which MLN4924 has entered phase I/II/III clinical trials for cancer treatment, such as acute myeloid leukemia, melanoma, lymphoma and solid tumors. Here, we systematically describe the structures and biological functions of the critical enzymes in neddylation, highlight the medicinal chemistry advances in the development of neddylation inhibitors and propose the perspectives concerning targeting neddylation for cancer and fibrotic diseases.© The author(s).