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 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

1.32727675E12
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
Neutrophils are a key component of the antitumor efficacy of topical chemotherapy with ingenol-3-angelate.
2006 Dec 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
Reactivation of HIV-1 from Latency by an Ingenol Derivative from Euphorbia Kansui.
2017 Aug 25
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 Fri Dec 15 16:35:06 UTC 2023
Edited
by admin
on Fri Dec 15 16:35:06 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 Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
WHO-VATC QD06BX02
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
EMA ASSESSMENT REPORTS PICATO (AUTHORIZED: KERATOSIS, ACTINIC)
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
WHO-ATC D06BX02
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
NDF-RT N0000184015
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
Code System Code Type Description
NDF-RT
N0000009176
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY Increased Cellular Death [PE]
EVMPD
SUB32495
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
WIKIPEDIA
Ingenol mebutate
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
INN
9006
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
HSDB
8308
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
SMS_ID
100000124379
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
PUBCHEM
6918670
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
USAN
TT-127
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
DRUG BANK
DB05013
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
EPA CompTox
DTXSID301025610
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
NCI_THESAURUS
C48398
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
MERCK INDEX
m11695
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
CHEBI
66913
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
ChEMBL
CHEMBL1863513
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
RXCUI
1242806
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY RxNorm
FDA UNII
7686S50JAH
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
CAS
75567-37-2
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
DRUG CENTRAL
4226
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
IUPHAR
7443
Created by admin on Fri Dec 15 16:35:06 UTC 2023 , Edited by admin on Fri Dec 15 16:35:06 UTC 2023
PRIMARY
Related Record Type Details
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Related Record Type Details
Structure of INGENOL
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
Structure of INGENOL
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
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