Ingenol Mebutate

75567-37-2

C25H34O6

DMSO : >= 100 mg/mL (232.27 mM)

TGF-beta/Smad; Epigenetics

Ingenol Mebutate is an active ingredient in Euphorbia peplus, acts as a potent PKC modulator, with K_is of 0.3, 0.105, 0.162, 0.376, and 0.171 nM for PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon, respectively, and has antiinflammatory and antitumor activity. IC50 & Target: Ki: 0.3 nM (PKC-alpha), 0.105 nM (PKC-beta), 0.162 nM (PKC-gamma), 0.376 nM (PKC-delta), 0.171 nM (PKC-epsilon)^[1] In Vitro: Ingenol Mebutate (Ingenol 3-angelate) is an active ingredient in Euphorbia peplus, acting as a potent PKC activator, with K_is of 0.3, 0.105, 0.162, 0.376, and 0.171 nM for PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon, respectively. Ingenol Mebutate also EC₅₀s of 13 +/- 2.4 nM (PKC-alpha), 4.37 +/- 0.4 nM (PKC-betaI), 10.5 +/- 2.2 nM (PKC-betaII), 38.6 +/- 2.9 nM (PKC-delta), 1.08 +/- 0.01 nM (PKC-epsilon), 0.9 +/- 0.13 nM (PKC-u) in WEHI-231 cells, 198 +/- 12.5 nM (PKC-alpha), 69.1 +/- 8.2 nM (PKC-betaI), 4.6 +/- 0.4 nM (PKC-epsilon) and 1 nM (PKC-u) in HOP-92 cells, 635 +/- 245 nM (PKC-alpha), 146 +/- 35 nM (PKC-betaI), 4.7 +/- 0.7 nM (PKC-delta), 1.1 +/- 0.5 nM (PKC-epsilon), and 30 nM (PKC-u) in Colo-205 cells. Ingenol Mebutate sensitizes WEHI-231 cells, HOP-92 and Colo-205 cells, with IC₅₀s of 1.41 +/- 0.255 nM, 3.24 +/- 2.01 nM, and 11.9 +/- 1.307 nM, respectively^[1]. Ingenol Mebutate (PEP005; 20 nM) actions are PKC-delta dependent, induces apoptosis in primary AML marrow blasts but not in normal myeloblasts^[2]. Ingenol Mebutate (PEP005) activates PKCdelta and inhibits PKCalpha. Colo205-R cells (IC₅₀: >10 uM) are >300-fold more resistant to Ingenol Mebutate than parental Colo205-S cells^[3].