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Cellular and Molecular Life Sciences

, Volume 73, Issue 5, pp 985–1001 | Cite as

Autophagy inhibitors

  • Benoit Pasquier
Review

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

Autophagy Autophagosomes PI3K PIK3C3/Vps34 ULK Lysosomotropic agent Hydroxychloroquine 

Abbreviations

ADME

Absorption, distribution, metabolism, excretion

AMPK

AMP-activated protein kinase

ATG

Autophagy-related genes or proteins

Beclin-1

Coiled-coil, myosin-like BCL2-ineracting protein

CQ

Chloroquine

DNA-PK

DNA-dependent protein kinase

FYVE

Fab1, YOTB, Vac1 and EEA1

GFP

Green fluorescent protein

HCQ

Hydroxychloroquine

LC3

Microtubule-associated protein light chain 3

mTOR

Mammalian target of rapamycine

mTORC1

Mammalian target of rapamycine complex 1

MEF

Mouse embryonic fibroblasts

PK

Pharmacokinetic

PI3K

Phosphoinositide 3-kinase

PIK3C3

Phosphatidylinositol 3-kinase, catalytic subunit type 3

PtdIns3K

Phosphatidylinositol 3-kinase

PtdIns3P

Phosphatidylinositol 3-phosphate

ULK

Unc-51-like kinase

ULK1

Unc-51-like kinase 1

Vps34

Vacuolar protein sorting 34

3-MA

3-methyladenine

Notes

Acknowledgments

I thank Baptiste Ronan, Magali Mathieu, Florence Fassy, Ellen Ross and Michael Shaw for their comments and suggestions during the preparation of this manuscript.

Compliance with ethical standards

Conflict of interest

BP is a Sanofi employee and also a shareholder of Sanofi stock.

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Copyright information

© Springer International Publishing 2015

Authors and Affiliations

  1. 1.SanofiVitry Sur SeineFrance

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