Wortmannin, a fungal metabolite, is a potent and selective inhibitor of PI 3-kinase. Wortmannin inhibits repair of DNA double-strand breaks in irradiated normal human cells. Wortmannin has an in vitro IC50 of around 5 nM, making it a more potent inhibitor than LY 294002 (sc-201426), another commonly used PI 3-kinase inhibitor. Wortmannin displays a similar potency in vitro for the class I, II, and III PI 3-kinase members, although it can also inhibit other PI 3-kinase-related enzymes such as FRAP (mTOR), DNA-PKCS, some phosphatidylinositol 4-kinases, myosin light chain kinase (MLCK) and mitogen-activated protein kinase (MAPK) at high concentrations. Wortmannin has also been reported to inhibit members of the polo-like kinase family with IC50 in the same range as for PI 3-kinase. 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 PI 3-kinase. Wortmannin is an inhibitor of Fnk and Plk.