ADAPALENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H28O3
Molecular Weight	412.5212
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COc1ccc(cc1C23CC4CC(CC(C4)C2)C3)-c5ccc6cc(ccc6c5)C(=O)O

InChI

InChIKey=LZCDAPDGXCYOEH-UHFFFAOYSA-N

InChI=1S/C28H28O3/c1-31-26-7-6-23(21-2-3-22-12-24(27(29)30)5-4-20(22)11-21)13-25(26)28-14-17-8-18(15-28)10-19(9-17)16-28/h2-7,11-13,17-19H,8-10,14-16H2,1H3,(H,29,30)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2000/20748lbl.pdf

Adapalene is a topical retinoid primarily used in the treatment of acne and is used (off-label) to treat keratosis pilaris as well as other skin conditions. Galderma currently markets it under the trade names Differin in some countries, and Adaferin in India. Adapalene acts on retinoid receptors. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization, and inflammatory processes all of which represent important features in the pathology of acne vulgaris. Mechanistically, adapalene binds to specific retinoic acid nuclear receptors but does not bind to the cytosolic receptor protein. Although the exact mode of action of adapalene is unknown, it is suggested that topical adapalene normalizes the differentiation of follicular epithelial cells resulting in decreased microcomedone formation.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Retinoic acid receptor gamma 9 Target ID: CHEMBL2003 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10651997	Agonist 1109
Retinoic acid receptor beta 8 Target ID: CHEMBL2008 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10651997	Agonist 1109

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acne vulgaris 16 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2000/20748lbl.pdf	Primary		Approved 4033	DIFFERIN Approved Use Adapalene gel, 0.1% is indicated for the topical treatment of acne vulgaris. Launch Date 8.3350081E11

C_max

Value	Dose	Co-administered	Analyte	Population
0.04 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10898827	6.8 mg 1 times / day multiple, topical dose: 6.8 mg route of administration: Topical experiment type: MULTIPLE co-administered:		ADAPALENE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.1 % 1 times / day multiple, topical Studied dose Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20415678 Page: p.1364	unhealthy, 12–26 n = 87 Health Status: unhealthy Condition: Acne Age Group: 12–26 Sex: M+F Population Size: 87 Sources: https://pubmed.ncbi.nlm.nih.gov/20415678 Page: p.1364	Disc. AE: Irritation skin... AEs leading to discontinuation/dose reduction: Irritation skin (severe, 9.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/20415678 Page: p.1364
0.3 % 1 times / day multiple, topical Recommended Dose: 0.3 %, 1 times / day Route: topical Route: multiple Dose: 0.3 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22007702 Page: p.59	unhealthy, 45 - 65 n = 40 Health Status: unhealthy Condition: Cutaneous photoaging Age Group: 45 - 65 Sex: F Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/22007702 Page: p.59	Disc. AE: Irritation skin... AEs leading to discontinuation/dose reduction: Irritation skin (severe, 7.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/22007702 Page: p.59
0.3 % 1 times / day multiple, topical Recommended Dose: 0.3 %, 1 times / day Route: topical Route: multiple Dose: 0.3 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Acne Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1	Disc. AE: Erythema, Scales... AEs leading to discontinuation/dose reduction: Erythema Scales Application site dryness Stinging Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
Irritation skin	severe, 9.2% Disc. AE	0.1 % 1 times / day multiple, topical Studied dose Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20415678 Page: p.1364	unhealthy, 12–26 n = 87 Health Status: unhealthy Condition: Acne Age Group: 12–26 Sex: M+F Population Size: 87 Sources: https://pubmed.ncbi.nlm.nih.gov/20415678 Page: p.1364
Irritation skin	severe, 7.5% Disc. AE	0.3 % 1 times / day multiple, topical Recommended Dose: 0.3 %, 1 times / day Route: topical Route: multiple Dose: 0.3 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22007702 Page: p.59	unhealthy, 45 - 65 n = 40 Health Status: unhealthy Condition: Cutaneous photoaging Age Group: 45 - 65 Sex: F Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/22007702 Page: p.59
Application site dryness	Disc. AE	0.3 % 1 times / day multiple, topical Recommended Dose: 0.3 %, 1 times / day Route: topical Route: multiple Dose: 0.3 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Acne Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1
Erythema	Disc. AE	0.3 % 1 times / day multiple, topical Recommended Dose: 0.3 %, 1 times / day Route: topical Route: multiple Dose: 0.3 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Acne Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1
Scales	Disc. AE	0.3 % 1 times / day multiple, topical Recommended Dose: 0.3 %, 1 times / day Route: topical Route: multiple Dose: 0.3 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Acne Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1
Stinging	Disc. AE	0.3 % 1 times / day multiple, topical Recommended Dose: 0.3 %, 1 times / day Route: topical Route: multiple Dose: 0.3 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Acne Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021753s004lbl.pdf Page: p.1

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31174	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31174
ChemicalBook	CB6771245	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6771245
MolPort	MolPort-003-986-211	https://www.molport.com/shop/molecule-link/MolPort-003-986-211
Selleck Chemicals	Adapalene	http://www.selleckchem.com/products/Adapalene.html
ZINC	ZINC000003784182	http://zinc15.docking.org/substances/ZINC000003784182
eMolecules	901333	https://www.emolecules.com/cgi-bin/more?vid=901333

PubMed

Title	Date	PubMed
The role of specific retinoid receptors in sebocyte growth and differentiation in culture.	2000 Feb	10651997
Adapalene in clinical practice.	2001 Oct	11845950
Adapalene gel 0.1%: effective and well tolerated in the topical treatment of acne vulgaris in Chinese patients.	2001 Oct	11845949
Adapalene gel 0.1% for topical treatment of acne vulgaris in African patients.	2001 Oct	11845948
Adapalene gel 0.1% is effective and well tolerated in acne patients in a dermatology practice setting.	2001 Oct	11845947
Efficacy and tolerance of adapalene cream 0.1% compared with its cream vehicle for the treatment of acne vulgaris.	2001 Oct	11845946
A multicenter, double-blind, randomized comparison study of the efficacy and tolerability of once-daily tazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acne vulgaris.	2002 Feb	12095066
Randomised, controlled trial of the efficacy and safety of adapalene gel 0.1% and tretinoin cream 0.05% in patients with acne vulgaris.	2002 Jul-Aug	12095880
Perioral dermatitis successfully treated with topical adapalene.	2002 Mar	12046830
Comparison of the effects of tretinoin, adapalene and collagenase in an experimental model of wound healing.	2002 Mar-Apr	11872410
The synthetic retinoid adapalene inhibits proliferation and induces apoptosis in colorectal cancer cells in vitro.	2003 Nov 10	14506747
Single-blind and comparative clinical study of the efficacy and safety of benzoyl peroxide 4% gel (BID) and adapalene 0.1% Gel (QD) in the treatment of acne vulgaris for 11 weeks.	2003 Sep	14522627
Cumulative irritancy comparison of adapalene gel 0.1% versus other retinoid products when applied in combination with topical antimicrobial agents.	2003 Sep	12963899
Adapalene: a review of its use in the treatment of acne vulgaris.	2004	15212561
[The clinical observation of treating acne vulgaris with "xiao cuo fang"].	2004 Apr	15307690
Skin tolerability and efficacy of combination therapy with hydrogen peroxide stabilized cream and adapalene gel in comparison with benzoyl peroxide cream and adapalene gel in common acne. A randomized, investigator-masked, controlled trial.	2004 Aug	15327558
Phototoxic effects of topical azelaic acid, benzoyl peroxide and adapalene were not detected when applied immediately before UVB to normal skin.	2004 Jul-Aug	15319156
Topical agents used in the management of hyperpigmentation.	2004 Jun-Jul	15334278
Topical retinoids in the management of acne: the best path to clear results.	2004 Oct	15543712
The efficacy and safety of adapalene gel 0.3% in the treatment of acne vulgaris: A randomized, multicenter, investigator-blinded, controlled comparison study versus adapalene gel 0.1% and vehicle.	2005 Aug	16209161
Fox fordyce disease in a prepubertal girl.	2005 Jan-Feb	15660912
Acne vulgaris.	2005 Jun	16135322
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Mechanism-based treatment of acne vulgaris: the value of combination therapy.	2005 May-Jun	15898282
Pseudoacne of the nasal crease in a patient with congenital deafness and pigmentary mosaicism.	2005 Nov-Dec	16354272
Comedolytic effect of a novel RARgamma-specific retinoid, ER36009: comparison with retinoic acid in the rhino mouse model.	2005 Nov-Dec	16280299
Adapalene gel 0.3% for the treatment of acne vulgaris: a multicenter, randomized, double-blind, controlled, phase III trial.	2006 Feb	16443054
Adapalene gel, 0.1%, as maintenance therapy for acne vulgaris: a randomized, controlled, investigator-blind follow-up of a recent combination study.	2006 May	16702497
Treatment of solar lentigines.	2006 May	16631967

Patents

Sample Use Guides

In Vivo Use Guide

Cream should be applied to affected areas of the skin, once daily at nighttime.

Route of Administration: Topical

In Vitro Use Guide

Explants of normal human skin and explants of acne patients were incubated with adapalene (10(-7) or 10(-6) M) for 24 h. Evaluation of epidermal expression by immunohistochemistry showed a decreased expression of TLR-2 and IL-10 in explants of normal skin and explants of acne with adapalene. On the contrary, adapalene increased CD1d expression in explants of acne patients. Thus, adapalene can modulate the epidermal immune system by increasing the CD1d expression and by decreasing the IL-10 expression by keratinocytes.

Name

Type

Language

ADAPALENE

Official Name

English

CD-271

Code

English

ADAPALENE [WHO-DD]

Common Name

English

DIFFERIN

Brand Name

English

ADAPALENE [MI]

Common Name

English

CD 271

Code

English

ADAPALENE [MART.]

Common Name

English

ADAPALENE [ORANGE BOOK]

Common Name

English

ADAPALENE [VANDF]

Common Name

English

2-NAPHTHALENECARBOXYLIC ACID, 6-(4-METHOXY-3-TRICYCLO(3.3.1.(SUP 13,7))DEC-1-YLPHENYL)-

Common Name

English

ADAPALENE [USP-RS]

Common Name

English

ADAPALENE [USP MONOGRAPH]

Common Name

English

ADAPALENE COMPONENT OF EPIDUO

Common Name

English

EPIDUO COMPONENT ADAPALENE

Common Name

English

ADAPALENE [EP MONOGRAPH]

Common Name

English

ADAPALENE [JAN]

Common Name

English

2-NAPHTHALENECARBOXYLIC ACID, 6-(4-METHOXY-3-TRICYCLO(3.3.1.1(SUP 3,7))DEC-1-YLPHENYL)-

Common Name

English

ADAPALENE [USAN]

Common Name

English

6-(3-(1-ADAMANTYL)-4-METHOXYPHENYL)-2-NAPHTHOIC ACID

Systematic Name

English

ADAPALENE [INN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QD10AD53