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Ingenol Mebutate is a diterpenoid derived from Euphorbia plant and a modulator of PKC with Ki values 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.In addition, Ingenol Mebutate is a cell death inducer with anticancer activity.Ingenol Mebutate has been shown to be an anticancer agent. Ingenol Mebutate is also an inducer of cell death and has anticancer activity.
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Source | Mol Cancer Ther (2015). Figure 4. Ingenol Mebutate |
| Method | qPCR | |
| Cell Lines | SCC cells | |
| Concentrations | 100 nmol/L | |
| Incubation Time | 24 h | |
| Results | In addition, we used either the PKC inhibitor AEB071 or a knockdown of PKCd, either alone or in combination with ingenol mebutate and analyzed the expression of ERK target genes. Either inhibition of PKC or knockdown of PKCd could prevent the upregulation of ERK target gene expression after ingenol mebutate treatment |
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Source | Mol Cancer Ther (2015). Figure 3. Ingenol Mebutate |
| Method | Western blotting | |
| Cell Lines | SCC13 cells | |
| Concentrations | 100 nmol/L | |
| Incubation Time | 24 h | |
| Results | Similar to our findings with the PKC inhibitor, we detected a rescue of cell viability upon ingenol mebutate treatment when PKCd was knocked down. A knockdown PKCa followed by ingenol mebutate treatment led only to a partial rescue, while PKCd knockdown could rescue the ingenol mebutate–treated cells completely |
| Cell Experiment | |
|---|---|
| Cell lines | T7 cell |
| Preparation method | Tumours were treated topically (on days 4 and 5 post tumour inoculation) with 30 μl of 0.25 % (w/v) ingenol mebutate or placebo gel (supplied by LEO Pharma A/S) using a positive displacement pipette, with the gel then spread over the tumour site. |
| Concentrations | 30 μl of 0.25 % (w/v) |
| Incubation time | 48 h |
| Animal Experiment | |
|---|---|
| Animal models | BALB/c nu−/nu− mice |
| Formulation | isopropanol-based gel |
| Dosages | 18 μg/kg |
| Administration | i.v. |
| Molecular Weight | 430.53 |
| Formula | C25H34O6 |
| CAS Number | 75567-37-2 |
| Solubility (25°C) | 41 mg/ml in CHCl3 |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
[2] Lebwohl M,et.al. N Engl J Med. Ingenol mebutate gel for actinic keratosis.
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Go 6983 is a fast acting, lipid soluble, broad spectrum protein kinase C inhibitor. |
| Staurosporine
Staurosporine (AM-2282) is a potent ATP-competitive kinase inhibitor with IC50 of 0.7, 7, 8.5, 6, 20 nM for PKC, PKA,PKG, p60v-src tyrosine protein kinase, CaM kinase II, respectively. |
| Zoledronic acid
Zoledronic Acid (Zoledronate) is a third-generation bisphosphonate (BP), with potent anti-resorptive activity. Zoledronic Acid inhibits the differentiation and apoptosis of osteoclasts. Zoledronic Acid also has anti-cancer effects. |
| Dequalinium Chloride
Dequalinium Chloride is a PKC inhibitor with IC50 of 7-18 μM, and also a selective blocker of apamin-sensitive K+ channels with IC50 of 1.1 μM. |
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