U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of INGENOL MEBUTATE

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

HIDE SMILES / InChI

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

Description
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

Targets

Primary TargetPharmacologyConditionPotency
30.0 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
PICATO

Approved Use

Indicated for the topical treatment of actinic keratosis.

Launch Date

1.32727675E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.332 nM
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

AUC

ValueDoseCo-administeredAnalytePopulation
1.43 ng × h/mL
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

Doses

DosePopulationAdverse 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)
Application site pain (severe, 1 patient)
Periorbital edema (severe, 1 patient)
Sources: Page: p. 52
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)
Skin exfoliation (1 patient)
Sources: Page: p. 53
AEs

AEs

AESignificanceDosePopulation
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

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence

Sample Use Guides

In Vivo Use Guide
Unknown
Route of Administration: Unknown
In Vitro Use Guide
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 Thu Jul 06 00:00:27 UTC 2023
Edited
by admin
on Thu Jul 06 00:00:27 UTC 2023
Record UNII
7686S50JAH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
INGENOL MEBUTATE
DASH   INN   MART.   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
INGENOL MEBUTATE [MART.]
Common Name English
2-BUTENOIC ACID, 2-METHYL-, (1AR,2S,5R,5AS,6S,8AS,9R,10AR)-1A,2,5,5A,6,9,10,10A-OCTAHYDRO-5,5A-DIHYDROXY-4-(HYDROXYMETHYL)-1,1,7,9-TETRAMETHYL-11-OXO-1H-2,8A-METHANOCYCLOPENTA(A)CYCLOPROPA(E)CYCLODECEN-6-YL ESTER, (2Z)-
Common Name English
INGENOL MEBUTATE [ORANGE BOOK]
Common Name English
PEP005
Code English
AGN204332
Code English
INGENOL MEBUTATE [USAN]
Common Name English
PEP-005
Code English
(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]cyclopropa[E]cyclodecen-6-yl (2Z)-2-methylbut-2-enoate
Common Name English
INGENOL MEBUTATE [VANDF]
Common Name English
PICATO
Brand Name English
INGENOL MEBUTATE [MI]
Common Name English
ingenol mebutate [INN]
Common Name English
Ingenol mebutate [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C274
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
WHO-VATC QD06BX02
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
EMA ASSESSMENT REPORTS PICATO (AUTHORIZED: KERATOSIS, ACTINIC)
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
WHO-ATC D06BX02
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
NDF-RT N0000184015
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
Code System Code Type Description
NDF-RT
N0000009176
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY Increased Cellular Death [PE]
EVMPD
SUB32495
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
WIKIPEDIA
Ingenol mebutate
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
INN
9006
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
HSDB
8308
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
SMS_ID
100000124379
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
PUBCHEM
6918670
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
USAN
TT-127
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
DRUG BANK
DB05013
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
EPA CompTox
DTXSID301025610
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
NCI_THESAURUS
C48398
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
MERCK INDEX
M11695
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
CHEBI
66913
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
ChEMBL
CHEMBL1863513
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
RXCUI
1242806
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY RxNorm
FDA UNII
7686S50JAH
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
CAS
75567-37-2
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
DRUG CENTRAL
4226
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
IUPHAR
7443
Created by admin on Thu Jul 06 00:00:27 UTC 2023 , Edited by admin on Thu Jul 06 00:00:27 UTC 2023
PRIMARY
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