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W-2990 Wortmannin, >98%

[KY 12420] [KY12420] [KY-12420]

M.W. 428.44

C23H24O8

[19545-26-7] RTECS:  CB9641000

M.I. 12:  10188

M.I. 14:  10053

Storage:  Store at or below 4 ºC.  Solubility:  Soluble in DMSO or ethanol.  Disposal:  A

View the MSDS for this product

• Isolated from the filamentous fungus, Penicillium funiculosum, wortmannin is a potent, irreversible, and specific inhibitor of phosphatidylinositol 3-kinase (PI3-K) with an IC50 of 2-5 nM.  Arcaro, A., and Wymann, M.P.  "Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses."  Biochem. J. 296:  297-301 (1993).  Wymann, M.P., and Arcaro, A.  "Platelet-derived growth factor-induced phosphatidylinositol 3-kinase activation mediates actin rearrangements in fibroblasts."  Biochem. J. 298:  517-520 (1994).  Powis, G., et al.  "Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase."  Cancer Res. 54:  2419-2423 (1994).  Wymann, M.P., et al.  "Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction."  Mol. Cell Biol. 16:  1722-1733 (1996).

• Inhibitor of both myosin light chain kinase (IC50 = 200 nM) and phosphatidylinositol 4-kinase at concentrations approximately 100-fold higher than the that required for PI3-K inhibition.  Nakanishi, S., et al.  "Wortmannin, a microbial product inhibitor of myosin light chain kinase."  J. Biol. Chem. 267:  2157-2163 (1992).

• Enhances radiation- or serum withdrawal-induced apoptosis through the inhibition of PI3-K/Akt signal transduction cascade and blocks the antiapoptotic effect of cytokines.  Krasilnikov, M., et al.  "Contribution of phosphatidylinositol 3-kinase to radiation resistance in human melanoma cells."  Mol. Carcinog. 24:  64-69 (1999).  Allen, M.P., et al.  "Growth arrest-specific gene 6/adhesion related kinase signaling promotes gonadotropin-releasing hormone neuronal survival via extracellular signal-regulated kinase (ERK) and Akt."  Mol. Endocrinol. 13:  191-201 (1999).  Morita, Y., et al.  "Requirement for phosphatidylinositol-3'-kinase in cytokine-mediated germ cell survival during fetal oogenesis in the mouse."  Endocrinology 140:  941-949 (1999).  Manna, S.K., and Aggarwal, B.B.  "Interleukin-4 down-regulates both forms of tumor necrosis factor receptor and receptor-mediated apoptosis, NFkappaB, AP-1, and c-Jun N-terminal kinase."  J. Biol. Chem. 273:  33333-33341 (1998).  Crowder, R.J., and Freeman, R.S.  "Phosphatidylinositol 3-kinase and Akt protein kinase are necessary and sufficient for the survival of nerve growth factor-dependent sympathetic neurons."  J. Neurosci. 18:  2933-2943 (1998).

• Wortmannin inhibition of PI3-K also blocks many of the short-term metabolic effects induced by insulin receptor activation in isolated rat adipocytes without affecting the insulin receptor tyrosine kinase activity.  Okada, T., et al.  "Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin."  J. Biol. Chem. 269:  3568-3573 (1994).  Moule, S.K., and Denton, R.M.  "Multiple signaling pathways involved in the metabolic effects of insulin."  Am. J. Cardiol. 80:  41A-49A (1997).

• Inhibits platelet activating factor-induced MAP kinase activation in guinea pig neutrophils (200 - 300 nM).  Ferby, I.M., et al.  "Wortmannin inhibits mitogen-activated protein kinase activation induced by platelet-activating factor in guinea pig neutrophils."  J. Biol. Chem. 269:  30485-30488 (1994).

• Inhibits phospholipase D activation.  Bonser, R.W., et al.  "Demethoxyviridin and wortmannin block phospholipase C and D activation in the human neutrophil."  Br. J. Pharmacol. 103:  1237-1241 (1991).

• Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.