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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2023

Open Access 01-12-2023 | Acute Myeloid Leukemia | Review

Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions

Authors: Dong-Jun Fu, Ting Wang

Published in: Journal of Hematology & Oncology | Issue 1/2023

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Abstract

NEDDylation, a post-translational modification through three-step enzymatic cascades, plays crucial roles in the regulation of diverse biological processes. NEDD8-activating enzyme (NAE) as the only activation enzyme in the NEDDylation modification has become an attractive target to develop anticancer drugs. To date, numerous inhibitors or agonists targeting NAE have been developed. Among them, covalent NAE inhibitors such as MLN4924 and TAS4464 currently entered into clinical trials for cancer therapy, particularly for hematological tumors. This review explains the relationships between NEDDylation and cancers, structural characteristics of NAE and multistep mechanisms of NEDD8 activation by NAE. In addition, the potential approaches to discover NAE inhibitors and detailed pharmacological mechanisms of NAE inhibitors in the clinical stage are explored in depth. Importantly, we reasonably investigate the challenges of NAE inhibitors for cancer therapy and possible development directions of NAE-targeting drugs in the future.
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Metadata
Title
Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions
Authors
Dong-Jun Fu
Ting Wang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2023
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-023-01485-7

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