Autophagy

Autophagy is a process by which a cell breaks down macromolecules in response to starvation or stress signals. While it is closely linked with apoptosis, autophagy is primarily characterized as a catabolic mechanism by which cellular energy homeostasis is maintained.

Products
Background
Literature

Inhibitors

Cat No Product Name / Activity
3771 Azithromycin
Autophagy inhibitor; antibiotic
1334 Bafilomycin A1
H+-ATPase (vacuolar) inhibitor; also inhibits autophagy
1544 (±)-Bay K 8644
L-type Ca2+ channel activator; inhibits autophagy
4109 Chloroquine diphosphate
Inhibits apoptosis and autophagy
2656 Concanamycin A
H+-ATPase (vacuolar) inhibitor
4417 DBeQ
Selective p97 ATPase inhibitor; blocks autophagosome maturation
4545 E 64d
Cathepsin inhibitor; interferes with autolysosomal digestion
0786 Edaravone
Autophagy inhibitor; also anti-ischemic and antioxidant
2473 GW 4064
Selective farnesoid X receptor (FXR) agonist; suppresses autophagy in nutrient-deprived hepatocytes
5648 Hydroxychloroquine sulfate
Autophagy inhibitor; also TLR9 inhibitor
1130 LY 294002 hydrochloride
Prototypical PI 3-kinase inhibitor; inhibits autophagic sequestration
3982 Mdivi 1
Autophagy inhibitor; also selective inhibitor of dynamin-related GTPase
3977 3-Methyladenine
Class III PI 3-kinase inhibitor; also inhibits autophagy
5153 ML 240
ATP-competitive inhibitor of p97 ATPase; impairs autophagosome maturation
5134 MRT 67307 dihydrochloride
Autophagy inhibitor; also salt inducible kinase (SIK) inhibitor
5780 MRT 68921 dihydrochloride
Autophagy inhibitor; potent ULK inhibitor
6180 NMS 873
Potent and selective p97 ATPase (VCP) allosteric inhibitor
1228 Nocodazole
Microtubule inhibitor; inhibits autophagosome-lysosome fusion
1190 Pepstatin A
Protease inhibitor; interferes with autolysosomal digestion
5197 Spautin 1
Inhibits autophagy; USP10 and USP13 inhibitor
1097 Taxol
Promotes assembly and inhibits disassembly of microtubules
1256 Vinblastine sulfate
Disrupts microtubules; inhibits autophagosome maturation
1232 Wortmannin
Potent, irreversible inhibitor of PI 3-kinase. Also inhibitor of PLK1
4686 Xanthohumol
p97 ATPase (VCP) inhibitor; impairs autophagosome maturation

Activators

Cat No Product Name / Activity
3336 A 769662
Autophagy activator; potent AMPK activator
1234 A23187, free acid
Causes ER stress; can be used to induce autophagy in mammalian cells
4095 Amiodarone hydrochloride
Causes mitochondrial fragmentation and cell death; stimulates autophagy
4846 Apicidin
Potent histone deacetylase inhibitor; induces autophagy
1231 Brefeldin A
Causes ER stress; induces autophagy in mammalian cells
4098 Carbamazepine
Reduces inositol levels; induces autophagy
0690 Clonidine hydrochloride
α2 agonist and I1 ligand; thought to enhance autophagy
1126 Dexamethasone
Anti-inflammatory glucocorticoid; also induces autophagy in ALL cell lines
3093 Dorsomorphin dihydrochloride
Induces autophagy via an AMPK inhibition-independent mechanism
3993 EB 1089
Vitamin D receptor agonist; induces autophagy in MCF-7 cells
6188 Everolimus
Autophagy activator; mTOR inhibitor
4808 FK 866 hydrochloride
Non-competitive and potent NAMPT inhibitor; induces apoptosis and autophagy
0741 GF 109203X
Protein kinase C inhibitor
4835 GPP 78 hydrochloride
NAMPT inhibitor; also induces autophagy
0681 L-690,330
Inositol monophosphatase inhibitor; induces autophagy independently of mTOR inhibition
2864 Metformin hydrochloride
Activator of LKB1/AMPK; activates autophagy
1391 NF 449
Highly selective P2X1 antagonist; G-selective antagonist
4079 Niclosamide
STAT3 inhibitor; also inhibits mTORC1 signaling. Stimulates autophagy in vitro
0600 Nimodipine
Ca2+ channel blocker (L-type)
0601 Nitrendipine
Ca2+ channel blocker (L-type)
4849 3-Nitropropionic acid
Irreversible mitochondrial respiratory complex II inhibitor; induces autophagy
6087 Perifosine
PKB/Akt inhibitor; induces autophagy
2930 PI 103 hydrochloride
Inhibitor of PI 3-kinase, mTOR and DNA-PK
1267 Pifithrin-α hydrobromide
p53 inhibitor
1292 Rapamycin
mTOR inhibitor; induces autophagy
1418 Resveratrol
Autophagy activator; also cyclooxygenase inhibitor
0695 Retinoic acid
Autophagy activator; also endogenous retinoic acid receptor agonist
0790 Rilmenidine hemifumarate
α2 agonist and I1 ligand; thought to enhance autophagy
1610 Rottlerin
Stimulates autophagy
4652 SAHA
Autophagy activator; also Class I and II HDAC inhibitor
4989 Salirasib
Ras inhibitor; also induces autophagy
4297 SMER 28
Positive regulator of autophagy
0959 Spermidine trihydrochloride
Autophagy activator; also NMDA receptor agonist
2706 Temozolomide
DNA-methylating antitumor agent; also induces autophagy
5264 Temsirolimus
Autophagy activator; mTOR inhibitor
1138 Thapsigargin
Causes ER stress; can be used to induce autophagy in mammalian cells
4247 Torin 1
Potent and selective mTOR inhibitor; induces autophagy in HeLa cells
4248 Torin 2
Autophagy activator; also potent and selective mTOR inhibitor
1406 Trichostatin A
Autophagy activator; potent histone deacetylase inhibitor
3516 Tunicamycin
Causes ER stress; can be used to induce autophagy
2815 Valproic acid, sodium salt
Reduces inositol levels; induces autophagy
0654 Verapamil hydrochloride
Ca2+ channel blocker (L-type)

Other

Cat No Product Name / Activity
5067 MRT 68601 hydrochloride
Potent TBK1 inhibitor; also inhibits autophagy

Autophagy is a process by which a cell breaks down macromolecules in response to starvation or stress signals. While it is closely linked with apoptosis, autophagy is primarily characterized as a catabolic mechanism by which cellular energy homeostasis is maintained, and by which cellular organelles and proteins are degraded.

Autophagy also occurs in response to similar stresses as those which induce apoptosis and several proapoptotic signals also induce autophagy - for example, TRAIL, ceramide and the DAPk (death-associated protein kinase) family. However, the way in which the cell is degraded differs: autophagy makes use of the cell's integral lysosomal machinery; apoptosis instead makes use of phagocytic cell lysosomes. These two mechanisms are characteristic of each process and help distinguish them under the microscope.

By enabling the degradation of organelles and macromolecules, autophagy helps provide cells with nutrients under starvation conditions. It assists in the removal of damaged mitochondria and proteins too large to be degraded by the ubiquitin-proteasomal system, as well as helping to maintain whole body homeostasis by removing irreversibly damaged cells. Under conditions such as infection and protein aggregation, this capacity to break down cellular components may also aid cell survival and alleviate neurodegeneration. Compromised autophagy can result in the aggregation of tau, α-synuclein and mutant huntingtin protein fragments, all of which are autophagy substrates and which are linked to neurodegenerative disease. In addition, defective autophagy has been linked to metabolic disorders (such as diabetes and obesity) and aging. Autophagy has also been linked to cancer development - it helps maintain nutrient-deprived cells located in the center of tumors. Autophagy can be used as a target for combination therapies, in particular those which inhibit autophagy and promote apoptosis instead. The roles of autophagy in cancer are complex and often contrasting, and may vary during disease progression. As a result, the targeting of autophagy to treat cancer is more likely to be context-dependent, unlike other tumor processes such as cell growth, angiogenesis and apoptosis.

Intracellular control over autophagy is largely transduced by mTOR and PI 3-K signaling. mTORC1 is directly responsible for autophagy regulation and acts as an autophagy suppressor downstream of the class I PI 3-K-Akt pathway. Nutrient deprivation suppresses kinase activity, thus activating autophagy; AMPK activation inhibits mTOR-dependent signaling, therefore stimulating autophagy. mTOR-independent pathways involved in autophagy also exist, including calpain and inositol, but their mechanisms are yet to be fully elucidated.

Literature for Autophagy

Cancer

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Neurodegeneration

Neurodegeneration Product Guide

A collection of over 275 products for neurodegeneration research, the guide includes research tools for the study of:

  • Alzheimer's disease
  • Parkinson's disease
  • Huntington's disease
Autophagy

Autophagy Scientific Review

Written by Patricia Boya and Patrice Codogno, this review summarizes the molecular mechanisms, physiology and pathology of autophagy. The role of autophagy in cell death and its links to disease are also discussed. Compounds available from Tocris are listed.

Autophagy

Autophagy Poster

Autophagy is a cellular process used by cells for degradation and recycling. Written by Patricia Boya and Patrice Codogno, this poster summarizes the molecular machinery, physiology and pathology of autophagy. Compounds available from Tocris are listed.

Programmed Cell Death

Programmed Cell Death Poster

There are two currently recognized forms of programmed cell death: apoptosis and necroptosis. This poster summarizes the signaling pathways involved in apoptosis, necroptosis and cell survival following death receptor activation, and highlights the influence of the molecular switch, cFLIP, on cell fate.