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Wortmannin

Wortmannin Unit size Cat. code Docs Qty Price
PI3K inhibitor
5 mg
tlrl-wtm
+-
$141.00
Discontinued

PI3K inhibitor - Autophagy Inhibitor

Inhibition of PI3K-III and autophagy by Wortmannin
Inhibition of PI3K-III and autophagy by Wortmannin

Wortmannin is a potent and selective inhibitor of phosphatidylinositol 3-kinase (PI3K) [1]. This family of enzymes is divided into three different PI3K classes (I, II, and III) which exhibit non‑redundant functions in cells [2]. PI3K plays an important role in many biological processes, including controlling the activation of mTOR, a key regulator of autophagy. Autophagy is a pathway by which cytoplasmic constituents are sequestered in a double-membrane-bound autophagosome and delivered to the lysosome for degradation.

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Mode of action:

Wortmannin is considered to be a pan-PI3K inhibitor targeting both PI3K class I and class III indiscriminately, while PI3K class II are less sensitive to wortmannin [3]. Specifically, it irreversibly inhibits PI3K class III, while its effects on PI3K class I are transient [4].
Wortmannin is widely used as an autophagy inhibitor based on its inhibitory effect on class III PI3K activity [4, 5]. Specifically, Wortmannin binds to the ATP active site and induces a conformational change in the catalytic domain [6]. Notably, Wortmannin is able to suppress autophagy regardless of nutrient status, unlike other autophagy inhibitors [4].

 

Key features:

  • Phosphoinositide 3-kinase (PI3K) inhibitor
  • An autophagy inhibitor

 

Read our reviewRead our review on Autophagy and Innate Immunity

 

References:

1. Arcaro A. & Wymann MP., 1993. Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses. Biochem. J. 296:297-301.
2. Jean S. & Kiger A.A., 2014. Classes of phosphoinositide 3-kinases at a glance. J Cell Sci. 127(5): 923-8.
3. Domin J. et al., 1997. Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin. Biochem J. 326(Pt1): 139-47.
4. Wu Y.T et al., 2010. Dual role of 3-Methyladenine in modulation of autophagy via different temporal patterns of inhibition on Class I and III phosphoinositide 3-kinase. J Biol Chem. 285(14):10850-61.

5. Blommaart E.F. et al., 1997. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur. J. Biochem. 243: 240–246.
6. Walker E.H. et al., 2000. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell. 6(4):909-19.

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Specifications

Working concentration: 20 nM-1 μM

Purity: ≥95% (LC)

Solubility: 10 mg/ml in DMSO

CAS number: 19545-26-7

Synonym: KY 12420

Molecular weight: 428.4 g/mol

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Contents

 Wortmannin is provided as a translucent film.

  • 5 mg Wortmannin

room temperature Wortmannin is shipped at room temperature.

store Upon receipt, store at -20°C.

Alert Wortmannin is light-sensitive. Protect from light.

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Details

Autophagy

Autophagy is an orchestrated homeostatic process to eliminate unwanted proteins and damaged organelles [1-3]. The autophagic process is also used to remove intracellular microbial pathogens. Several signaling pathways sense different types of cell stress, ranging from nutrient deprivation to microbial invasion, and converge to regulate autophagy at multiple stages of the process. Autophagy starts with phagophore (also known as isolation membrane) formation, a step is initiated by a protein complex comprising UNC-51-like kinase 1 or 2 (ULK1 or ULK2) and Atg (autophagy-related genes) proteins. ULK1/2 then phosphorylates components of the class III phosphatidylinositol 3-kinase (PI3K) complex, whose formation is driven by Beclin 1. The phagophore elongates and isolates its cargo inside a closed structure termed autophagosome. The fusion of the lysosome with the autophagosome as an autophagolysosome (or autolysosome) allows the degradation of its contents.

 

References

1. Levine B. & Kroemer G., 2008. Autophagy in the pathogenesis of disease. Cell. 132(1):27-42.
2. Mizushima N. et al., 2008. Autophagy fights disease through cellular self-digestion. Nature. 451(7182):1069-75.
3. Netea-Maier R.T. et al., 2016, Modulation of inflammation by autophagy: Consequences for human disease. Autophagy. 12(2): 245–260.

 

Chemical structure of Wortmannin

Chemical structure of Wortmannin

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Citations

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