Skip to main content
. 2021 Oct 27;20:140. doi: 10.1186/s12943-021-01423-6

Table 2.

Inhibitors of autophagy

Drug Systematic name Known targets Status Limitations References
MRT68921 N-[3-[[5-Cyclopropyl-2-[(1,2,3,4-tetrahydro-2-methyl-6-isoquinolinyl)amino]-4-pyrimidinyl]amino]propyl]-cyclobutanecarboxamide dihydrochloride ULK1, ULK2, NUAK1 Preclinical Mitotic dysregulation; crosstalk with endocytic pathways [166, 202, 203, 260]
3-MA 3-Methyladenine PI3Ks preclinical non-selectivity; activation of autophagy in a longer period of treatment; cytotoxicity; crosstalk with endocytic pathways [206, 210–212]
Wortmannin (1alpha,11alpha)-11-(Acetyloxy)-1-(methoxymethyl)-2-oxaandrosta-5,8-dieno(6,5,4-bc)furan-3,7,17-trione PI3Ks, DNA-PK preclinical failed clinical translation due to drug-delivery challenges; proteosynthesis inhibition; crosstalk with endocytic pathways [209, 211, 261]
LY294002 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one PI3Ks preclinical activation of autophagy; proteosynthesis inhibition; crosstalk with endocytic pathways [207, 209, 211, 212]
Spautin-1 C43, 6-Fluoro-N-[(4-fluorophenyl)methyl]-4-quinazolinamine USP10, USP13 preclinical ROS-mediated DNA damag; Beclin1 degradation; crosstalk with endocytic pathways [224, 228, 229, 262]
Autophinib 6-Chloro-N-(5-methyl-1H-pyrazol-3-yl)-2-(4-nitrophenoxy)-pyrimidinamine VPS34 preclinical pleiotropic impact of VPS34 inhibition; impaired T-cell–mediated immunity [99, 231]
SAR405 (8S)-9-[(5-chloro-3-pyridinyl)methyl]-6,7,8,9-tetrahydro-2-[(3R)-3-methyl-4-morpholinyl]-8-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one VPS34 preclinical pleiotropic impact of VPS34 inhibition; defects in endosomal trafficking; impaired T-cell–mediated immunity [99, 232, 233]
VPS34-IN1 1-((2-((2-chloropyridin-4-yl)amino)-4'-(cyclopropylmethyl)-[4,5'-bipyrimidin]-2'-yl)amino)-2-methylpropan-2-ol VPS34 preclinical pleiotropic impact of VPS34 inhibition; defects in endosomal trafficking; impaired T-cell–mediated immunity [99, 232]
Cpd18 3-methyl-6-(3-methylpiperidin-1-yl)-3H-purine omegasomes preclinical toxicity; decreased ubiquitin/proteasome-dependent proteolysis [210, 234]
Chloroquine 4-N-(7-chloroquinolin-4-yl)-1-N,1-N-diethylpentane-1,4-diamine autolysosomes; lysosomes; endosomes 21 clinical trials phase 1 or 2; only one phase 3 study (NCT00224978) lysosomal stress; crosstalk with endocytic pathways; uptake may differ based on pH [223, 236, 241, 244, 246, 263]
HCQ 2-[4-[(7-chloroquinolin-4-yl)amino]pentyl-ethylamino]ethanol autolysosomes; lysosomes; endosomes 94 clinical trials; only one phase 2/3 study (NCT03008148) uptake may differ based on pH [227, 239, 264]
Bafilomycin A1 (3Z,5E,7R,8S,9S,11E,13E,15S,16R)-16-[(2S,3R,4S)-4-[(2R,4R,5S,6R)-2,4-dihydroxy-5-methyl-6-propan-2-yloxan-2-yl]-3-hydroxypentan-2-yl]-8-hydroxy-3,15-dimethoxy-5,7,9,11-tetramethyl-1-oxacyclohexadeca-3,5,11,13-tetraen-2-one V-ATPase preclinical cytotoxicity and caspase activation; effects on Golgi trafficking; crosstalk with endocytic pathways [210, 251, 265]
YM201636 6-amino-N-[3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenyl]pyridine-3-carboxamide PIKfyve preclinical block of protein sorting; crosstalk with endocytic pathways and exocytosis [257, 259]
Vacuolin-1 2-N-[(E)-(3-iodophenyl)methylideneamino]-6-morpholin-4-yl-4-N,4-N-diphenyl-1,3,5-triazine-2,4-diamine PIKfyve preclinical block of protein sorting; crosstalk with endocytic pathways and exocytosis [257, 259]
Apilimod mesylate methanesulfonic acid;N-[(E)-(3-methylphenyl)methylideneamino]-6-morpholin-4-yl-2-(2-pyridin-2-ylethoxy)pyrimidin-4-amine PIKfyve preclinical block of protein sorting; crosstalk with endocytic pathways and exocytosis [257, 259]
EACC ethyl (2-(5-nitrothiophene-2-carboxamido) thiophene-3-carbonyl) carbamate. STX17 preclinical crosstalk with endocytic pathways and exocytosis [236, 237]