tcsc2971 Ingenol Mebutate

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-α, PKC-β, PKC-γ, PKC-δ, and PKC-ε, respectively, and has antiinflammatory and antitumor activity.

IC50 & Target: Ki: 0.3 nM (PKC-α), 0.105 nM (PKC-β), 0.162 nM (PKC-γ), 0.376 nM (PKC-δ), 0.171 nM (PKC-ε)^[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-α, PKC-β, PKC-γ, PKC-δ, and PKC-ε, respectively. Ingenol Mebutate also EC₅₀s of 13 ± 2.4 nM (PKC-α), 4.37 ± 0.4 nM (PKC-βI), 10.5 ± 2.2 nM (PKC-βII), 38.6 ± 2.9 nM (PKC-δ), 1.08 ± 0.01 nM (PKC-ε), 0.9 ± 0.13 nM (PKC-μ) in WEHI-231 cells, 198 ± 12.5 nM (PKC-α), 69.1 ± 8.2 nM (PKC-βI), 4.6 ± 0.4 nM (PKC-ε) and 1 nM (PKC-μ) in HOP-92 cells, 635 ± 245 nM (PKC-α), 146 ± 35 nM (PKC-βI), 4.7 ± 0.7 nM (PKC-δ), 1.1 ± 0.5 nM (PKC-ε), and 30 nM (PKC-μ) 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-δ dependent, induces apoptosis in primary AML marrow blasts but not in normal myeloblasts^[2]. Ingenol Mebutate (PEP005) activates PKCδ and inhibits PKCα. Colo205-R cells (IC₅₀: >10 μM) are >300-fold more resistant to Ingenol Mebutate than parental Colo205-S cells^[3].