Wortmannin

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Wortmannin
Identifiers
CAS number [19545-26-7]
PubChem 5691
SMILES CC(=O)OC1CC2(C(CCC2=O)C3=C1C4 (C(OC(=O)C5=COC(=C54)C3=O)COC)C)C
Properties
Molecular formula C23H24O8
Molar mass 428.43186
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Wortmannin, a furanosteroid metabolite of the fungi Penicillium funiculosum, [Talaromyces (Penicillium) wortmannii]][1], is a specific inhibitor of phosphoinositide 3-kinases (PI3Ks). It has an in vitro inhibitory concentration (IC50) of around 5 nM, making it a more potent inhibitor than LY294002, another commonly used PI3K inhibitor. It displays a similar potency in vitro for the class I, II, and III PI3K members although it can also inhibit other PI3K-related enzymes such as mTOR, DNA-PK, some phosphatidylinositol 4-kinases, myosin light chain kinase (MLCK) and mitogen-activated protein kinase (MAPK) at high concentrations [2],[3] Wortmannin has also been reported to inhibit members of the polo-like kinase family with IC50 in the same range as for PI3K. [4]. The half-life of wortmannin in tissue culture is about 10 minutes. Wortmannin is a commonly used cell biology reagent that has been used previously in research to inhibit DNA repair, receptor-mediated endocytosis and cell proliferation[citation needed].

[edit] Background: [5]Phosphoinositide-3-kinase

Phosphoinositide-3-kinase (PI-3-K) activates an important cell survival signaling pathway, and constitutive activation is seen in ovarian, head and neck, urinary tract, cervical and small cell lung cancer. PI-3-K signaling is attenuated by the phosphatase activity of the tumor suppressor PTEN that is absent in a number of human cancers. Inhibiting PI-3-K presents the opportunity to inhibit a major cancer cell survival signaling pathway and to overcome the action of an important deleted tumor suppressor, providing antitumor activity and increased tumor sensitivity to a wide variety of drugs.

Wortmannin is a known and potent PI-3-K inhibitor; however its severe hepatotoxicity and chemical instability make it an impractical pharmaceutical agent.

[edit] References

  1. ^ Source: www.fermentek.co.il/wortmannin.htm
  2. ^ Vanhaesebroeck B et al., (2001) Synthesis and function of 3-phosphorylated inositol lipids. Annu Rev Biochem.
  3. ^ Ferby I et al., 1996. Adv Exp Med Biol. PAF-induced MAPK activation is inhibited by wortmannin in neutrophils and macrophages.
  4. ^ Liu Y et al., 2007. J. Biol Chem 282(4): 2505-11 Polo-like Kinases Inhibited by Wortmannin: Labeling Site and Downstream Effects
  5. ^ Source: [1]

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