Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C25H34O6 |
Molecular Weight | 430.5339 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 8 / 8 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12C[C@@H](C)[C@]34C=C(C)[C@H](OC(=O)C(\C)=C/C)[C@@]3(O)[C@H](O)C(CO)=C[C@H](C4=O)[C@]1([H])C2(C)C
InChI
InChIKey=VDJHFHXMUKFKET-WDUFCVPESA-N
InChI=1S/C25H34O6/c1-7-12(2)22(29)31-21-13(3)10-24-14(4)8-17-18(23(17,5)6)16(20(24)28)9-15(11-26)19(27)25(21,24)30/h7,9-10,14,16-19,21,26-27,30H,8,11H2,1-6H3/b12-7-/t14-,16+,17-,18+,19-,21+,24+,25+/m1/s1
Molecular Formula | C25H34O6 |
Molecular Weight | 430.5339 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 8 / 8 |
E/Z Centers | 1 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/25970561http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202833s007lbl.pdfCurator's Comment: http://www.dermnetnz.org/topics/ingenol-mebutate-gel/; http://www.ncbi.nlm.nih.gov/pubmed/25115145; https://www.ncbi.nlm.nih.gov/pubmed/?term=24672213; http://www.ncbi.nlm.nih.gov/pubmed/?term=26225771;
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25970561http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202833s007lbl.pdf
Curator's Comment: http://www.dermnetnz.org/topics/ingenol-mebutate-gel/; http://www.ncbi.nlm.nih.gov/pubmed/25115145; https://www.ncbi.nlm.nih.gov/pubmed/?term=24672213; http://www.ncbi.nlm.nih.gov/pubmed/?term=26225771;
Ingenol mebutate is a substance found in the sap of the plant Euphorbia peplus. Ingenol mebutate gel was developed as a short-course topical therapy for actinic keratosis and non-melanoma skin cancer. It was approved under the trade name Picato by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the topical treatment of actinic keratosis in two gel formulations of different strengths for use on either the face and scalp (0.015%) or the trunk and extremities (0.05%). Ingenol mebutate may offer several advantages over other AK treatments currently on the market, including a shorter duration of use, faster resolution of lesions, and a favorable side-effect profile. It was shown in several randomized, double-blind, vehicle-controlled studies that applied topically for 2 to 3 days ingenol mebutate gel is effective for treatment of actinic keratoses. The mechanism of action by which Picato gel induces cell death in treating AK lesions is unknown. It is presumed to involve primary necrosis then neutrophil-mediated inflammation and antibody-dependent cell death of residual disease cells. Also ingenol mebutate activates various protein kinase C (PKC) isoforms, thereby inducing apoptosis in some tumor cells, including myeloid leukemia cells, melanoma cells, and basal cell carcinoma cells. The PKC family consists of signaling isoenzymes that regulate many cell processes including proliferation, differentiation, and apoptosis. Ingenol mebutate (PEP005) has also been found to be useful for reactivating latent HIV virus in cells taken from individuals who have tested negative for signs of the disease following extended courses of anti-retroviral drugs, raising the possibility that this drug may be used to expose the last traces of virus, and thus potentially provide a permanent cure for HIV infection. Research is ongoing to determine whether the effects observed in vitro are also seen in animal models, with a view to eventual human trials for this application.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2093867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1727380 |
30.0 µM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | PICATO Approved UseIndicated for the topical treatment of actinic keratosis. Launch Date1.32727675E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.332 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28524709 |
0.127 mg 1 times / day multiple, topical dose: 0.127 mg route of administration: Topical experiment type: MULTIPLE co-administered: |
INGENOL MEBUTATE blood | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.43 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28524709 |
0.127 mg 1 times / day multiple, topical dose: 0.127 mg route of administration: Topical experiment type: MULTIPLE co-administered: |
INGENOL MEBUTATE blood | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
0.015 % 1 times / day multiple, topical Recommended Dose: 0.015 %, 1 times / day Route: topical Route: multiple Dose: 0.015 %, 1 times / day Sources: Page: p. 52 |
unhealthy, 61 years n = 1 Health Status: unhealthy Age Group: 61 years Sex: M Population Size: 1 Sources: Page: p. 52 |
Disc. AE: Eye pain, Application site pain... AEs leading to discontinuation/dose reduction: Eye pain (severe, 1 patient) Sources: Page: p. 52Application site pain (severe, 1 patient) Periorbital edema (severe, 1 patient) |
0.25 % 1 times / day multiple, topical Highest studied dose Dose: 0.25 %, 1 times / day Route: topical Route: multiple Dose: 0.25 %, 1 times / day Sources: Page: p. 53 |
unhealthy n = 1 Health Status: unhealthy Condition: superficial basal cell carcinoma Population Size: 1 Sources: Page: p. 53 |
Disc. AE: Lymphangitis... AEs leading to discontinuation/dose reduction: Lymphangitis (1 patient) Sources: Page: p. 53 |
0.05 % 1 times / day multiple, topical Recommended Dose: 0.05 %, 1 times / day Route: topical Route: multiple Dose: 0.05 %, 1 times / day Sources: Page: p. 53 |
unhealthy n = 1 Health Status: unhealthy Condition: nodular basal cell carcinoma Population Size: 1 Sources: Page: p. 53 |
Disc. AE: Erythema, Skin exfoliation... AEs leading to discontinuation/dose reduction: Erythema (1 patient) Sources: Page: p. 53Skin exfoliation (1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Application site pain | severe, 1 patient Disc. AE |
0.015 % 1 times / day multiple, topical Recommended Dose: 0.015 %, 1 times / day Route: topical Route: multiple Dose: 0.015 %, 1 times / day Sources: Page: p. 52 |
unhealthy, 61 years n = 1 Health Status: unhealthy Age Group: 61 years Sex: M Population Size: 1 Sources: Page: p. 52 |
Eye pain | severe, 1 patient Disc. AE |
0.015 % 1 times / day multiple, topical Recommended Dose: 0.015 %, 1 times / day Route: topical Route: multiple Dose: 0.015 %, 1 times / day Sources: Page: p. 52 |
unhealthy, 61 years n = 1 Health Status: unhealthy Age Group: 61 years Sex: M Population Size: 1 Sources: Page: p. 52 |
Periorbital edema | severe, 1 patient Disc. AE |
0.015 % 1 times / day multiple, topical Recommended Dose: 0.015 %, 1 times / day Route: topical Route: multiple Dose: 0.015 %, 1 times / day Sources: Page: p. 52 |
unhealthy, 61 years n = 1 Health Status: unhealthy Age Group: 61 years Sex: M Population Size: 1 Sources: Page: p. 52 |
Lymphangitis | 1 patient Disc. AE |
0.25 % 1 times / day multiple, topical Highest studied dose Dose: 0.25 %, 1 times / day Route: topical Route: multiple Dose: 0.25 %, 1 times / day Sources: Page: p. 53 |
unhealthy n = 1 Health Status: unhealthy Condition: superficial basal cell carcinoma Population Size: 1 Sources: Page: p. 53 |
Erythema | 1 patient Disc. AE |
0.05 % 1 times / day multiple, topical Recommended Dose: 0.05 %, 1 times / day Route: topical Route: multiple Dose: 0.05 %, 1 times / day Sources: Page: p. 53 |
unhealthy n = 1 Health Status: unhealthy Condition: nodular basal cell carcinoma Population Size: 1 Sources: Page: p. 53 |
Skin exfoliation | 1 patient Disc. AE |
0.05 % 1 times / day multiple, topical Recommended Dose: 0.05 %, 1 times / day Route: topical Route: multiple Dose: 0.05 %, 1 times / day Sources: Page: p. 53 |
unhealthy n = 1 Health Status: unhealthy Condition: nodular basal cell carcinoma Population Size: 1 Sources: Page: p. 53 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000PharmR.pdf#page=24 Page: 24.0 |
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1727380
C3H 10T1/2 cells were inoculated into 24-well plates at a density of 2 x l0^4 cells/well in 0.5 ml of DMEM plus 10% fetal bovine serum. After 24 h, cells were labeled for 18 h with 0.5 mkCi/ml [3Hlarachidonic acid (60 to 100 Ci/mmol). After the labeling period, the medium was removed and cultures were washed 4 times with fresh medium. Cells were treated with ingenol or PDBu (in DMEM plus serum) for the indicated times, and 25-gil aliquots of supernatant medium were removed for determination of radioactivity using a scmtillation counter
Substance Class |
Chemical
Created
by
admin
on
Edited
Thu Jul 06 00:00:27 UTC 2023
by
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on
Thu Jul 06 00:00:27 UTC 2023
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Record UNII |
7686S50JAH
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C274
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WHO-VATC |
QD06BX02
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EMA ASSESSMENT REPORTS |
PICATO (AUTHORIZED: KERATOSIS, ACTINIC)
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WHO-ATC |
D06BX02
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NDF-RT |
N0000184015
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N0000009176
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PRIMARY | Increased Cellular Death [PE] | ||
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SUB32495
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Ingenol mebutate
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9006
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8308
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100000124379
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6918670
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TT-127
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DB05013
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DTXSID301025610
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C48398
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M11695
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66913
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CHEMBL1863513
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1242806
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7686S50JAH
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75567-37-2
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4226
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7443
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Related Record | Type | Details | ||
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BINDER->LIGAND |
BINDING
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Related Record | Type | Details | ||
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METABOLITE ACTIVE -> PRODRUG |
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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