Autophagy inhibitors

Cell Mol Life Sci. 2016 Mar;73(5):985-1001. doi: 10.1007/s00018-015-2104-y. Epub 2015 Dec 11.

Abstract

Autophagy is a lysosome-dependent mechanism of intracellular degradation. The cellular and molecular mechanisms underlying this process are highly complex and involve multiple proteins, including the kinases ULK1 and Vps34. The main function of autophagy is the maintenance of cell survival when modifications occur in the cellular environment. During the past decade, extensive studies have greatly improved our knowledge and autophagy has exploded as a research field. This process is now widely implicated in pathophysiological processes such as cancer, metabolic, and neurodegenerative disorders, making it an attractive target for drug discovery. In this review, we will summarize the different types of inhibitors that affect the autophagy machinery and provide some potential therapeutic perspectives.

Keywords: Autophagosomes; Autophagy; Hydroxychloroquine; Lysosomotropic agent; PI3K; PIK3C3/Vps34; ULK.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Autophagy-Related Protein-1 Homolog
  • Chloroquine / analogs & derivatives
  • Chloroquine / chemistry
  • Chloroquine / pharmacology
  • Drug Discovery* / methods
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Pyrimidinones / chemistry
  • Pyrimidinones / pharmacology
  • Signal Transduction / drug effects*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrimidinones
  • Chloroquine
  • Autophagy-Related Protein-1 Homolog
  • Protein-Serine-Threonine Kinases
  • ULK1 protein, human