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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H37NO7
Molecular Weight 499.5959
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of INGENOL DISOXATE

SMILES

CCC1=NOC(CC)=C1C(=O)O[C@H]2C(C)=C[C@@]34[C@H](C)C[C@@H]5[C@H]([C@H](C=C(CO)[C@@H](O)[C@]23O)C4=O)C5(C)C

InChI

InChIKey=GLIUZQUNUNICGS-XUBYYPQFSA-N
InChI=1S/C28H37NO7/c1-7-18-20(19(8-2)36-29-18)25(33)35-24-13(3)11-27-14(4)9-17-21(26(17,5)6)16(23(27)32)10-15(12-30)22(31)28(24,27)34/h10-11,14,16-17,21-22,24,30-31,34H,7-9,12H2,1-6H3/t14-,16+,17-,21+,22-,24+,27+,28+/m1/s1

HIDE SMILES / InChI
Molecular Formula C28H37NO7
Molecular Weight 499.5959
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 8
E/Z Centers 0
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 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
Substance Class Chemical
Created
by admin
on Mon Mar 31 23:28:20 GMT 2025
Edited
by admin
on Mon Mar 31 23:28:20 GMT 2025
Record UNII
3B100VJ4ZW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ingenol disoxate [INN]
Preferred Name English
INGENOL DISOXATE
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
(1aR,2S,3Z,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 3,5-diethylisoxazole-4-carboxylate
Systematic Name English
Ingenol disoxate [WHO-DD]
Common Name English
LEO43204
Code English
LEO-43204
Code English
INGENOL DISOXATE [USAN]
Common Name English
INGENOL 3-(3,5-DIETHYLISOXAZOLE-4-CARBOXYLATE)
Common Name English
4-ISOXAZOLECARBOXYLIC ACID, 3,5-DIETHYL-, (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
Systematic Name English
Code System Code Type Description
NCI_THESAURUS
C123379
Created by admin on Mon Mar 31 23:28:20 GMT 2025 , Edited by admin on Mon Mar 31 23:28:20 GMT 2025
PRIMARY
FDA UNII
3B100VJ4ZW
Created by admin on Mon Mar 31 23:28:20 GMT 2025 , Edited by admin on Mon Mar 31 23:28:20 GMT 2025
PRIMARY
SMS_ID
100000174968
Created by admin on Mon Mar 31 23:28:20 GMT 2025 , Edited by admin on Mon Mar 31 23:28:20 GMT 2025
PRIMARY
DRUG BANK
DB15109
Created by admin on Mon Mar 31 23:28:20 GMT 2025 , Edited by admin on Mon Mar 31 23:28:20 GMT 2025
PRIMARY
PUBCHEM
57410862
Created by admin on Mon Mar 31 23:28:20 GMT 2025 , Edited by admin on Mon Mar 31 23:28:20 GMT 2025
PRIMARY
CAS
1383547-60-1
Created by admin on Mon Mar 31 23:28:20 GMT 2025 , Edited by admin on Mon Mar 31 23:28:20 GMT 2025
PRIMARY
USAN
DE-94
Created by admin on Mon Mar 31 23:28:20 GMT 2025 , Edited by admin on Mon Mar 31 23:28:20 GMT 2025
PRIMARY
INN
10127
Created by admin on Mon Mar 31 23:28:20 GMT 2025 , Edited by admin on Mon Mar 31 23:28:20 GMT 2025
PRIMARY
Related Record Type Details
Structure of INGENOL
ACTIVE MOIETY
NIH
NCATS
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