Application of Novel Degraders Employing Autophagy for Expediting Medicinal Research

J Med Chem. 2023 Feb 9;66(3):1700-1711. doi: 10.1021/acs.jmedchem.2c01712. Epub 2023 Jan 30.

Abstract

Targeted protein degradation (TPD) technology is based on a unique pharmacological mechanism that has profoundly revolutionized medicinal research by overcoming limitations associated with traditional small-molecule drugs. Autophagy, a mechanism for intracellular waste disposal and recovery, is an important biological process in medicinal research. Recently, studies have demonstrated that several emerging autophagic degraders can treat human diseases. Herein we summarize the progress in medicinal research on autophagic degraders, including autophagosome-tethering compounds (ATTEC), autophagy-targeting chimeras (AUTAC), and AUTOphagy-TArgeting chimeras (AUTOTAC), for treating human diseases. These autophagic degraders exhibit excellent potential for treating neurodegenerative diseases. Our research on autophagic degraders provides a new avenue for medicinal research on TPD via autophagy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagosomes / metabolism
  • Autophagy*
  • Humans
  • Neurodegenerative Diseases* / drug therapy
  • Neurodegenerative Diseases* / metabolism
  • Proteolysis