Wortmannin

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CASNo=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
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Formula=C₂₃H₂₄O₈
MolarMass=428.43186
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Wortmannin, a furanosteroid metabolite of the fungi "Penicillium funiculosum", " [Talaromyces (Penicillium) wortmannii] " [Source: [http://www.fermentek.co.il/wortmannin.htm www.fermentek.co.il/wortmannin.htm] ] , is a specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks). It has an "in vitro" inhibitory concentration ("IC"₅₀) 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 [ Vanhaesebroeck B "et al.", (2001) Synthesis and function of 3-phosphorylated inositol lipids. Annu Rev Biochem. ] ^, [Ferby I "et al"., 1996. Adv Exp Med Biol. PAF-induced MAPK activation is inhibited by wortmannin in neutrophils and macrophages.] Wortmannin has also been reported to inhibit members of the polo-like kinase family with "IC"₅₀ in the same range as for PI3K. [Liu Y "et al.", 2007. J. Biol Chem 282(4): 2505-11 Polo-like Kinases Inhibited by Wortmannin: Labeling Site and Downstream Effects] . The half-life of wortmannin in tissue culture is about 10 minutes due to the presence of the highly reactive C20 carbon that is also responsible for its ability to covalently inactivate PI3K. 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 Fact|date=February 2007.

Background: [Source: [http://www.prolx.com/content/PX866.asp] ] 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.

References

External links

Vendors' product pages
* [http://www.fermentek.co.il/wortmannin.htm Wortmannin product page] from Fermentek