4.7 Review

Targeting Atg4B for cancer therapy: Chemical mediators

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 209, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2020.112917

Keywords

Autophagy; atg4B; Drug target; Cancer; Small molecule modulators

Funding

  1. National Natural Science Foundation of China [81573290, U1603123,91853109, 81903502]
  2. Sichuan Provincial Science and Technology Department [20YYJC3921]

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Atg4B is a pivotal protein family in macroautophagy/autophagy that regulates the autophagy process and plays a key role in the development of human cancers. Efforts are being made to explore Atg4B inhibitors or activators for the development of novel drugs targeting Atg4B for potential clinical applications.
Atg4, a pivotal macroautophagy/autophagy-related cysteine protein family, which regulate autophagy through either cleaving Atg8 homologs for its further lipidation or delipidating Atg8 homologs from the autophagosome. There are four homologs, Atg4A, Atg4B, Atg4C, and Atg4D. Among them, an increasing amount of evidence indicates that Atg4B possessed superior catalytic efficiency toward the Atg8 substrate, as well as regulates autophagy process and plays a key role in the development of several human cancers. Recently, efforts have been contributed to the exploration of Atg4B inhibitors or activators. In this review, we comprehensively clarify the function of Atg4B in autophagy and cancer biology, as well as the relationship between pharmacological function and structure-activity of small molecule drugs targeting Atg4B. The development of novel drugs targeting Atg4B could be well applied in the clinical practice. (C) 2020 Elsevier Masson SAS. All rights reserved.

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