Targeting cullin neddylation for cancer and fibrotic diseases.

Abstract

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.

• Authors: Zhang-Xu He, Wei-Guang Yang, Dan Zengyangzong, Ge Gao, Qian Zhang, Hong-Min Liu, Wen Zhao, Li-Ying Ma
• Journal: Theranostics (Theranostics) Vol. 13 Issue 14 Pg. 5017-5056 ( 2023) ISSN: 1838-7640 [Electronic] Australia
• PMID: 37771770 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• Cullin Proteins
• NEDD8 Protein

Topics

• Humans
• Cullin Proteins (metabolism)
• NEDD8 Protein (metabolism)
• Neoplasms (drug therapy, pathology)
• Lymphoma
• Protein Processing, Post-Translational