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Autophagy Inducers and Inhibitors

Small molecules able to inhibit or induce autophagic activity provide a mechanism to modulate and study autophagy at the single cell and organismal level. In contrast to genetic models, pharmacological agents allow temporal and dose control. Moreover, often the effects of autophagy modulating agents are reversible. For animal model systems, targeted delivery of small molecules-autophagy modulators to specific organs and tissues may represent a significant advantage.

Small Molecule Modulators Mode of Action
3-Methyladenine AMPK inhibitor
(±)-Bay K 8644 L-type Ca2+ channel activator
Spautin 1 USP10 and USP13 inhibitor
LY 294002*, Wortmannin* VPS34 inhibitor
MRT 67307, MRT 68921 ULK inhibitor
Simvastatin*, A 769662* AMPK activator
Rapamycin*, Torins (1 and 2) Everolimus, PI 103 mTOR inhibitor
Dexamethasone Anti-inflammatory glucocorticoid; may act via mTOR pathway
L-690,330 Inositol monophosphatase inhibitor; independent of mTOR inhibition
Dorsomorphin AMPK inhibition-independent
A23187 free acid*, Brefeldin A* Thapsigargin*, Tunicamycin* Causes ER stress
Amiodarone Causes mitochondrial fragmentation and cell death
GF 109203X Protein kinase C inhibitor
NF 449* Highly selective P2X1 antagonist; Gsα-selective antagonist
Perifosine PKB/AKT inhibitor

*Commonly used modulators. Autophagy modulators available at Tocris:

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