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

C\C=C(\C)C(=O)O[C@H]1C(C)=C[C@@]23[C@H](C)C[C@@H]4[C@H]([C@H](C=C(CO)[C@@H](O)[C@]12O)C3=O)C4(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

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 is an extremely weak PKC (protein kinase C) activator, with potent anticancer activity. Ingenol derivatives have received constant and multidisciplinary attention on account of their pleiotropic pattern of biological activity. This includes activation of PKC (protein kinase C), tumor-promotion, anticancer, and anti-HIV properties, and the possibility of dissecting co-cancerogenic and clinically useful activities has been demonstrated. Certain ingenol esters show powerful anticancer activity, and a structure-activity relationship model to discriminate between their apoptotic and non-apoptotic properties has been developed.

Originator

Approval Year

2012
608
Targets

Targets

Primary TargetPharmacologyConditionPotency
Activator
1447
 30.0 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8583
PICATO

Approved Use

Indicated for the topical treatment of actinic keratosis.

Launch Date

2012
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
unhealthy, 61 years
Health Status: unhealthy
Age Group: 61 years
Sex: M
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Disc. AE: Lymphangitis...
AEs leading to
discontinuation/dose reduction:
Lymphangitis (1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Disc. AE: Erythema, Skin exfoliation...
AEs leading to
discontinuation/dose reduction:
Erythema (1 patient)
Skin exfoliation (1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
unhealthy, 61 years
Health Status: unhealthy
Age Group: 61 years
Sex: M
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
unhealthy, 61 years
Health Status: unhealthy
Age Group: 61 years
Sex: M
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
unhealthy, 61 years
Health Status: unhealthy
Age Group: 61 years
Sex: M
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2252

inducer
1087
inhibitor
2438

inducer
440
inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
2153

CYP2A6
879

CYP2B6
926

CYP2C8
1057

CYP2C19
2057

CYP2E1
1060
P-gp
2052
CYP1A2
832
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
2333
 no
CYP1A2
2333
 no
CYP2A6
911
 no
CYP2B6
1160
 no
CYP2C19
2141
 no
CYP2C8
1117
 no
CYP2C9
2497
 no
CYP2C9
2497
 no
CYP2D6
2546
 no
CYP2E1
1146
 no
CYP3A4
2633
 no
CYP3A4
2633
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
2052
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:66913
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:66913
ZINC
ZINC000056898854
http://zinc15.docking.org/substances/ZINC000056898854
PubMed

PubMed

TitleDatePubMed
Reactivation of HIV-1 from Latency by an Ingenol Derivative from Euphorbia Kansui.
2017-08-25
Ingenol mebutate gel for actinic keratosis.
2012-03-15
PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: results of a randomized, double-blind, vehicle-controlled, multicentre, phase IIa study.
2009-02
Neutrophils are a key component of the antitumor efficacy of topical chemotherapy with ingenol-3-angelate.
2006-12-01
HIV type 1 inhibition by protein kinase C modulatory compounds.
2006-09
Characterization of the interaction of ingenol 3-angelate with protein kinase C.
2004-05-01
Patents

Patents

20090292017
3
20110257262
3
20120295970
3
20120295971
3
20120309827
3
20130158110
3
20130177952
3
20130225677
3
20130225678
3
JP2017075113
3

Sample Use Guides

In Vivo Use Guide
For application of up to one contiguous skin area of approximately 25 cm^2 (5 cm x 5 cm) using one unit dose tube. For actinic keratosis on the face or scalp apply Picato gel, 0.015% to the affected area once daily for 3 consecutive days. For actinic keratosis on the trunk or extremities apply Picato gel 0.05% to the affected area once daily for 2 consecutive days
Route of Administration: Topical
In Vitro Use Guide
Unknown
Name Type Language
INGENOL MEBUTATE
DASH   INN   MART.   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
PICATO
Preferred 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
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 Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
WHO-VATC QD06BX02
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
EMA ASSESSMENT REPORTS PICATO (AUTHORIZED: KERATOSIS, ACTINIC)
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
WHO-ATC D06BX02
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
NDF-RT N0000184015
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
Code System Code Type Description
NDF-RT
N0000009176
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY Increased Cellular Death [PE]
EVMPD
SUB32495
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
WIKIPEDIA
Ingenol mebutate
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
INN
9006
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
HSDB
8308
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
SMS_ID
100000124379
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
PUBCHEM
6918670
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
USAN
TT-127
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
DRUG BANK
DB05013
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
EPA CompTox
DTXSID301025610
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
NCI_THESAURUS
C48398
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
MERCK INDEX
m11695
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
CHEBI
66913
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
ChEMBL
CHEMBL1863513
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
RXCUI
1242806
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY RxNorm
FDA UNII
7686S50JAH
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
CAS
75567-37-2
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
DRUG CENTRAL
4226
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
IUPHAR
7443
Created by admin on Mon Mar 31 18:31:55 GMT 2025 , Edited by admin on Mon Mar 31 18:31:55 GMT 2025
PRIMARY
ACTIVE MOIETY
Structure of INGENOL
SUBSTANCE RECORD
Structure of INGENOL MEBUTATE
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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