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Autophagy inhibitors

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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.

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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

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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.

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    Benoit Pasquier

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

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Pasquier, B. Autophagy inhibitors. Cell. Mol. Life Sci. 73, 985–1001 (2016). https://doi.org/10.1007/s00018-015-2104-y

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