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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

[H][C@@]12C[C@@H](C)[C@]34C=C(C)[C@H](OC(=O)C5=C(CC)ON=C5CC)[C@@]3(O)[C@H](O)C(CO)=C[C@]([H])(C4=O)[C@]1([H])C2(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

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
595
Targets

Targets

Primary TargetPharmacologyConditionPotency
Activator
1430
 30.0 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8429
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
Page: p. 52
unhealthy, 61 years
n = 1
Health Status: unhealthy
Age Group: 61 years
Sex: M
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 53
unhealthy
n = 1
Health Status: unhealthy
Condition: superficial basal cell carcinoma
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 53
Disc. AE: Lymphangitis...
AEs leading to
discontinuation/dose reduction:
Lymphangitis (1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 53
unhealthy
n = 1
Health Status: unhealthy
Condition: nodular basal cell carcinoma
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 53
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
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 52
unhealthy, 61 years
n = 1
Health Status: unhealthy
Age Group: 61 years
Sex: M
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 52
unhealthy, 61 years
n = 1
Health Status: unhealthy
Age Group: 61 years
Sex: M
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 52
unhealthy, 61 years
n = 1
Health Status: unhealthy
Age Group: 61 years
Sex: M
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 53
unhealthy
n = 1
Health Status: unhealthy
Condition: superficial basal cell carcinoma
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 53
unhealthy
n = 1
Health Status: unhealthy
Condition: nodular basal cell carcinoma
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 53
unhealthy
n = 1
Health Status: unhealthy
Condition: nodular basal cell carcinoma
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf
Page: p. 53
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1587

inducer
781
inhibitor
1767

inducer
389
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2A6
707

CYP2B6
810

CYP2C8
911

CYP2C19
1478

CYP2E1
882
P-gp
1537
CYP1A2
701
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 no
CYP1A2
1692
 no
CYP2A6
739
 no
CYP2B6
1001
 no
CYP2C19
1553
 no
CYP2C8
965
 no
CYP2C9
1819
 no
CYP2C9
1819
 no
CYP2D6
1891
 no
CYP2E1
970
 no
CYP3A4
1925
 no
CYP3A4
1925
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1537
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
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
Characterization of the interaction of ingenol 3-angelate with protein kinase C.
2004 May 1
HIV type 1 inhibition by protein kinase C modulatory compounds.
2006 Sep
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 Feb
Ingenol mebutate gel for actinic keratosis.
2012 Mar 15
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 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
ingenol disoxate [INN]
Common Name 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 Sat Dec 16 10:50:58 GMT 2023 , Edited by admin on Sat Dec 16 10:50:58 GMT 2023
PRIMARY
FDA UNII
3B100VJ4ZW
Created by admin on Sat Dec 16 10:50:58 GMT 2023 , Edited by admin on Sat Dec 16 10:50:58 GMT 2023
PRIMARY
SMS_ID
100000174968
Created by admin on Sat Dec 16 10:50:58 GMT 2023 , Edited by admin on Sat Dec 16 10:50:58 GMT 2023
PRIMARY
DRUG BANK
DB15109
Created by admin on Sat Dec 16 10:50:58 GMT 2023 , Edited by admin on Sat Dec 16 10:50:58 GMT 2023
PRIMARY
PUBCHEM
57410862
Created by admin on Sat Dec 16 10:50:58 GMT 2023 , Edited by admin on Sat Dec 16 10:50:58 GMT 2023
PRIMARY
CAS
1383547-60-1
Created by admin on Sat Dec 16 10:50:58 GMT 2023 , Edited by admin on Sat Dec 16 10:50:58 GMT 2023
PRIMARY
USAN
DE-94
Created by admin on Sat Dec 16 10:50:58 GMT 2023 , Edited by admin on Sat Dec 16 10:50:58 GMT 2023
PRIMARY
INN
10127
Created by admin on Sat Dec 16 10:50:58 GMT 2023 , Edited by admin on Sat Dec 16 10:50:58 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of INGENOL
SUBSTANCE RECORD
Structure of INGENOL DISOXATE
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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