A PKC activator
Ingenol is a diterpenoid related to phorbol, derived from the milkweed plant E. peplus.1 It is a protein kinase C activator that displays a Ki value of 30 μM and an ED50 value of 27 μM in vitro.2,3 Most ingenol esters are tumor-promoting.4 However, ingenol mebutate possesses anti-tumor activity when used topically for actinic keratosis.5
1.Wender, P.A., Koehler, K.F., Sharkey, N.A., et al.Analysis of the phorbol ester pharmacophore on protein kinase C as a guide to the rational design of new classes of analogsProc. Natl. Acad. Sci. USA83(12)4214-4218(1986) 2.Hasler, C.M., Acs, G., and Blumberg, P.M.Specific binding to protein kinase C by ingenol and its induction of biological responsesCancer Res.52(1)202-208(1992) 3.Vogg, G., Mattes, E., Rothenburger, J., et al.Tumor promoting diterpenes from Euphorbia leuconeura LPhytochemistry51(2)289-295(1999) 4.Nelson, T.J., and Alkon, D.L.Neuroprotective versus tumorigenic protein kinase C activatorsTrends Biochem. Sci.34(3)136-145(2009) 5.Lebwohl, M., Swanson, N., Anderson, L.L., et al.Ingenol mebutate gel for actinic keratosisN. Engl. J. Med.366(11)1010-1019(2012)
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