. Author manuscript; available in PMC: 2012 Dec 10.

Published in final edited form as: Nat Rev Drug Discov. 2012 Sep;11(9):709–730. doi: 10.1038/nrd3802

Table 2.

Selected drugs and compounds that modulate autophagy

Compounds	Company	Mechanism of action	Refs
*Autophagy inducers*
Rapamycin	Sigma-Aldrich	Induces autophagy by inhibiting mTORC1	44,49, 246
PP242	Sigma-Aldrich	Induces autophagy by inhibiting mTORC1	247
Torin 1	Tocris Bioscience	Directly inhibits both mTORC1 and mTORC2	176
Metformin	Sigma-Aldrich	Upregulates AMPK, which promotes autophagy by inducing ULK1 phosphorylation	248,249
BH3 mimetics (ABT-737)	Selleckchem	Disrupts the inhibitory interaction between the BH3 domain of beclin 1 and BCL-2, stimulating the beclin 1-dependent allosteric activation of the pro-autophagic lipid kinase PIK3C3	250
Xestospongin B	Sigma-Aldrich	Disrupts the molecular complex formed by the Ins(1,4,5)P₃ receptor and beclin 1	251
l-NAME	Cayman Chemical	Decreases nitric oxide formation to induce autophagy	63
Rilmenidine^*	Tocris Bioscience	Lowers cAMP levels	49,66
Clonidine	Sigma-Aldrich	Lowers cAMP levels to induce autophagy	49
PI-103 hydrochloride	Tocris Bioscience	Highly selective class I PI3K inhibitor and ATP-competitive mTOR inhibitor	179
Lithium, L-690330	Enzo Life Sciences	Lower inositol and Ins(1,4,5)P₃ levels	182
Carbamazepine	Sigma-Aldrich	Lowers inositol and Ins(1,4,5)P₃ levels	49,182
Resveratrol	Sigma-Aldrich	Activates sirtuin 1 (histone deacetylase) and inhibits 70 kDa ribosomal protein S6 kinase	252–254
Verapamil	Sigma-Aldrich	Lowers intracytosolic Ca²⁺ levels	49
EGFR antagonists, erlotinib hydrochloride	Roche	Inhibits the PI3K–AKT–mTOR signalling pathway	255,256
Sodium valproate	Sigma-Aldrich	Lowers inositol and Ins(1,4,5)P₃ levels	49,182
Spermidine	Sigma-Aldrich	Postulated to affect expression of ATG genes	186
Vinblastine	Sigma-Aldrich	Inhibits microtubule formation	257
Nocodazole	Sigma-Aldrich	Inhibits microtubule formation and blocks autophagosome–lysosome fusion	258,259
Bafilomycin A1	Merck Millipore	Specific inhibitor of V-ATPase; inhibits autophagosome–lysosome fusion	44,243
Chloroquine^‡	Sigma-Aldrich	Inhibits autophagosome–lysosome fusion	4,118
Hydroxychloroquine^‡	Sigma-Aldrich	Inhibits autophagosome–lysosome fusion	60,118
Spautin-1	Cellagen Technology	Lowers beclin 1 levels by promoting its ubiquitylation	200

AMPK, AMP-activated protein kinase; ATG, autophagy-related; BCL-2, B cell lymphoma 2; BH3, BCL-2 homology 3; cAMP, cyclic AMP; EGFR, epidermal growth factor receptor; Ins(1,4,5)P₃, inositol-1,4,5-trisphosphate; l-NAME, N-l-arginine methyl ester; mTOR, mammalian target of rapamycin; mTORC1, mTOR complex 1; PI3K, phosphoinositide 3-kinase; PIK3C3, class III PI3K (also known as VPS34); spautin-1, specific and potent autophagy inhibitor 1; ULK1, UNC51-like kinase 1; V-ATPase, vacuolar ATPase.

Phase I safety trial underway.

^‡

These drugs are undergoing Phase I/II clinical trials as autophagy inhibitors in patients with different types of cancers. See the ClinicalTrials.gov website for a list of US National Institutes of Health (NIH)-sponsored clinical trials.