By phosphorylating phosphatidylinositol, phosphoinositide 3-kinases (PI3K), activates diverse cellular functions, including cell growth, differentiation, survival, and motility. Wortmannin is a potent, cell-permeable, and irreversible inhibitor of PI3K enzymes (IC50 = 1-10 nM). However, the class II PI3Ks from Drosophila, murine, and human differ in sensitivity to wortmannin (IC50 = 5, 50, 450 nM, respectively).1 Wortmannin also inhibits polo-like kinase 1 (IC50 = 24 nM)2 and polo-like kinase 3 (IC50 = 49 nM)3, as well as mTOR, DNA-PK, PI4K, MLCK, and p38 MAPK at 50 to 100 fold higher concentrations than that needed for PI3K inhibition.
1
Fruman, D.A., Meyers, R.E., and Cantley, L.C. Phosphoinositide kinases. Annu Rev Biochem67481-507(2008).
2
Liu, Y., Shreder, K.R., Gai, W., et al. Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase. Chem Biol1299-107(2005).
3
Liu, Y., Jiang, N., Wu, J., et al. Polo-like kinases inhibited by wortmannin. Labeling site and downstream effects. J Biol Chem282(4)2505-2511(2007).
Fruman, D.A., Meyers, R.E., and Cantley, L.C. Phosphoinositide kinases. Annu Rev Biochem67481-507(2008).
Liu, Y., Shreder, K.R., Gai, W., et al. Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase. Chem Biol1299-107(2005).
Liu, Y., Jiang, N., Wu, J., et al. Polo-like kinases inhibited by wortmannin. Labeling site and downstream effects. J Biol Chem282(4)2505-2511(2007).
Wortmannin is available in the following screening
library: