DB05013 - Ingenol Mebutate
| Identification | |
|---|---|
| Name | Ingenol Mebutate |
| Accession Number | DB05013 |
| Type | small molecule |
| Description | Ingenol mebutate was approved by the FDA in January 2012, and it is marketed under the name Picato(R). Picato gel is indicated for the topical treatment of actinic keratosis. Before approval, ingenol mebutate was called PEP005 as an investigational drug. PEP005 is a selective small molecule activator of protein kinase C (PKC) extracted from the plant Euphorbia peplus, whose sap has been used as a traditional medicine for the treatment of skin conditions including warts and cancer. PEP005 also has potent anti-leukemic effects, inducing apoptosis in myeloid leukemia cell lines and primary AML cells at nanomolar concentrations. |
| Structure |
|
| Categories (*) | |
| Molecular Weight | 430.5339 |
| Groups | approved |
| Monoisotopic Weight | 430.23553882 |
| Pharmacology | |
| Indication | For the topical treatment of actinic keratosis. |
| Mechanism of action | The exact mechanism of action of ingenol mebutate in actinic keratosis is unknown. It is presumed to involve primary necrosis then neutrophil-mediated inflammation and antibody-dependent cell death of residual disease cells. Additionally in early studies, PEP005 was shown to be an effective activator of PKC-delta and PKC-delta translocation into nucleus and membranes. PEP005 also downregulates the expression and activity of PKC-alpha. PEP005 induced modulation of PKCs leads to Ras/Raf/MAPK and p38 activation and AKT/PKB inhibition. |
| Absorption | Since ingenol mebutate is a topical treatment, the systemic absorption is less than 0.1 ng/mL. |
| Protein binding | There is no plasma protein binding quantity since ingenol mebutate is a topical treatment |
| Biotransformation | There is no metabolism of Picato since ingenol mebutate is a topical treatment, and ingenol mebutate does not inhibit or induce a majority of the cytochrome P450 (CYP) enzymes. |
| Route of elimination | There is no route of elimination since ingenol mebutate is a topical treatment. |
| Toxicity | The most common adverse reactions are local skin reactions at the application site, headache, periorbital edema,and nasopharyngitis. |
| Affected organisms |
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| Interactions | |
| Drug Interactions | Not Available |
| Food Interactions |
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Targets
| Protein kinase C delta type | |
|---|---|
| Name | Protein kinase C delta type |
| Gene Name | PRKCD |
| Pharmacological action | unknown |
| Actions | ligand |
| References |
|
| DTHybrid score | 1.7031 |
| Protein kinase C alpha type | |
| Name | Protein kinase C alpha type |
| Gene Name | PRKCA |
| Pharmacological action | unknown |
| Actions | ligand |
| References |
|
| DTHybrid score | 0.5872 |