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 15 Target ID: CHEMBL2003 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10651997	Agonist 2470
Retinoic acid receptor beta 15 Target ID: CHEMBL2008 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10651997	Agonist 2470

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acne vulgaris 30 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2000/20748lbl.pdf	Primary		Approved 8043	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
Adapalene in the treatment of African patients.	2001	11843232
A comparison of adapalene gel 0.1% vs. tretinoin gel 0.025% in the treatment of acne vulgaris in China.	2001	11843231
Adapalene gel 0.1% for topical treatment of acne vulgaris in African patients.	2001 Oct	11845948
Epithelial malignancies in organ transplant patients: clinical presentation and new methods of treatment.	2002	12079221
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
Potential anti-inflammatory effects of topical retinoids and retinoid analogues.	2002 May-Jun	12201351
Optimizing treatment with topical tazarotene.	2003	12627995
The rationale for using a topical retinoid for inflammatory acne.	2003	12553848
Cumulative irritancy potential of adapalene cream 0.1% compared with adapalene gel 0.1% and several tretinoin formulations.	2003 Dec	14700217
Management of acne.	2003 Jan	12540312
Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial.	2003 Jul	12833014
Axillary granular parakeratosis.	2003 Jul-Aug	14738100
13-cis-retinoic acid competitively inhibits 3 alpha-hydroxysteroid oxidation by retinol dehydrogenase RoDH-4: a mechanism for its anti-androgenic effects in sebaceous glands?	2003 Mar 28	12646198
Retinoids: fascinating up-and-coming scenario.	2003 May	12773802
Clinical review: topical retinoids.	2003 Oct	14619325
Cumulative irritancy comparison of adapalene gel 0.1% versus other retinoid products when applied in combination with topical antimicrobial agents.	2003 Sep	12963899
Is combined oral and topical therapy better than oral therapy alone in patients with moderate to moderately severe acne vulgaris? A comparison of the efficacy and safety of lymecycline plus adapalene gel 0.1%, versus lymecycline plus gel vehicle.	2003 Sep	12963898
A review of the use of combination therapies for the treatment of acne vulgaris.	2003 Sep	12963896
Spotlight on adapalene in acne vulgaris.	2004	15554742
Adapalene: a review of its use in the treatment of acne vulgaris.	2004	15212561
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
An unusual late onset closed-comedone naevus: successful therapy with light cautery and a topical retinoid.	2004 Jan	14754653
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
Potentiated anticancer effects on hepatoma cells by the retinoid adapalene.	2004 May 10	15105045
Facial tolerability of topical retinoid therapy.	2004 Nov-Dec	15624747
Meta-analysis of topical tazarotene in the treatment of mild to moderate acne.	2004 Oct	15543714
Retinoid therapy for acne. A comparative review.	2005	15675886
Cumulative irritation potential of adapalene 0.1% cream and gel compared with tretinoin microsphere 0.04% and 0.1%.	2005 Apr	15916222
Topical retinoids in inflammatory acne: a retrospective, investigator-blinded, vehicle-controlled, photographic assessment.	2005 Feb	15811485
Mechanisms of the comedolytic and anti-inflammatory properties of topical retinoids.	2005 Jan-Feb	15696984
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Benzoyl peroxide, adapalene, and their combination in the treatment of acne vulgaris.	2005 Mar	15863861
Adapalene vs. metronidazole gel for the treatment of rosacea.	2005 Mar	15807740
Milia en plaque.	2005 Mar	15752313
The potential immunomodulatory effects of topical retinoids.	2005 Mar 1	15748544
Prescribing patterns for topical retinoids within NAMCS data.	2005 Mar-Apr	15776774
Tazarotene cream versus adapalene cream in the treatment of facial acne vulgaris: a multicenter, double-blind, randomized, parallel-group study.	2005 Mar-Apr	15776771
Minimal important difference (MID) of the Dermatology Life Quality Index (DLQI): results from patients with chronic idiopathic urticaria.	2005 May 20	15907211
Mechanism-based treatment of acne vulgaris: the value of combination therapy.	2005 May-Jun	15898282
Combination therapy with adapalene gel 0.1% and doxycycline for severe acne vulgaris: a multicenter, investigator-blind, randomized, controlled study.	2005 May-Jun	15891249
Pseudoacne of the nasal crease in a patient with congenital deafness and pigmentary mosaicism.	2005 Nov-Dec	16354272
The potential risks of nanomaterials: a review carried out for ECETOC.	2006 Aug 14	16907977
Adapalene gel 0.3% for the treatment of acne vulgaris: a multicenter, randomized, double-blind, controlled, phase III trial.	2006 Feb	16443054
The MORE trial: effectiveness of adapalene gel 0.1% in real-world dermatology practices.	2006 Jul	16910026
The results of the MORE trial: overview.	2006 Jul	16910025
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