Ingenol mebutate

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Ingenol mebutate
Ingenol 3-angelate.svg
Systematic (IUPAC) name
(1aR,2S,5R,5aS,6S,8aS,9R,10aR)-5,5a-Dihydroxy-4-(hydroxymethyl)-1,1,7,9-tetramethyl-11-oxo-1a,2,5,5a,6,9,10,10a-octahydro-1H-2,8a-methanocyclopenta[a]cyclpropa[e][10]annulen-6-yl (2Z)-2-methylbut-2-enoate
Clinical data
Trade names Picato
AHFS/Drugs.com entry
Pregnancy cat. C (US)
Legal status -only (US)
Routes Topical (gel)
Pharmacokinetic data
Bioavailability Below detection level
Identifiers
CAS number 75567-37-2
ATC code D06BX02
PubChem CID 6918670
ChemSpider 26325194
ChEBI CHEBI:66913 YesY
Synonyms PEP005, ingenol-3-angelate
Chemical data
Formula C25H34O6 
Mol. mass 430.534 g/mol

Ingenol mebutate (ingenol-3-angelate, LEO Pharma trade name Picato) is a substance found in the sap of the plant Euphorbia peplus[1] and an inducer of cell death. A gel formulation of the drug has been approved by the U.S. Food and Drug Administration (FDA)[2] and by the European Medicines Agency (EMA)[3] for the topical treatment of actinic keratosis. Two different strengths of the gel are approved for use on either the face and scalp (0.015%) or the trunk and extremities (0.05%), respectively.[4]

Results from four multicenter, randomized, double-blind studies have shown that ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses.[5]

Adverse effects[edit]

Irritations of the application site are very common. This includes redness, scaling, crusting, pain, pruritus, and sometimes infection. Other side effects include eye irritation such as periorbital edema (3% of patients in studies), headache (2%) and nasopharyngitis (running nose, 2%).[6]

Interactions[edit]

As ingenol mebutate is practically not absorbed through the skin, interactions with oral drugs are unlikely.[7][8]

Chemistry[edit]

The substance is an ester of the diterpene ingenol and angelic acid. A 14-step synthesis of (+)-ingenol from (+)-3-carene, which is a relatively inexpensive constituent of turpentine, was published in July 2013.[9]

References[edit]

  1. ^ Fallen RS, Gooderham M (2012). "Ingenol mebutate: An introduction". Skin Therapy Lett 17 (2): 1–3. PMID 22358305. 
  2. ^ Picato Drug Details at Drugs@FDA
  3. ^ European Public Assessment Report (EPAR) for Picato
  4. ^ Picato® Gel label at Drugs@FDA
  5. ^ Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B (2012). "Ingenol Mebutate Gel for Actinic Keratosis". N Engl J Med 336 (11): 1010–1019. doi:10.1056/NEJMoa1111170. PMID 22417254. 
  6. ^ Drugs.com: Picato Side Effects in Detail
  7. ^ Picato FDA Professional Drug Information
  8. ^ Haberfeld, H, ed. (2013). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. 
  9. ^ Jorgensen, L.; McKerrall, S. J.; Kuttruff, C. A.; Ungeheuer, F.; Felding, J.; Baran, P. S. (2013). "14-Step Synthesis of (+)-Ingenol from (+)-3-Carene". Science 341 (6148): 878–882. doi:10.1126/science.1241606. PMID 23907534.  edit