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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.

SUBMITTER: He ZX

PROVIDER: S-EPMC10526667 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Targeting cullin neddylation for cancer and fibrotic diseases.

He Zhang-Xu ZX Yang Wei-Guang WG Zengyangzong Dan D Gao Ge G Zhang Qian Q Liu Hong-Min HM Zhao Wen W Ma Li-Ying LY

Theranostics 20230904 14

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 fo ...[more]

PMID: 37771770

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