ADAPALENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H28O3
Molecular Weight	412.5201
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(C=C(C=C1)C2=CC3=C(C=C2)C=C(C=C3)C(O)=O)C45CC6CC(CC(C6)C4)C5

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

Molecular Formula	C28H28O3
Molecular Weight	412.5201
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 18 Target ID: CHEMBL2003 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10651997	Agonist 2637
Retinoic acid receptor beta 18 Target ID: CHEMBL2008 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10651997	Agonist 2637

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acne vulgaris 34 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2000/20748lbl.pdf	Primary		Approved 8307	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 biochemistry and the evolution of a new topical retinoid for treatment of acne.	2001	11843234
The integral role of topical and oral retinoids in the early treatment of acne.	2001	11843233
Are 2 combined antimicrobial mechanisms better than 1 for the treatment of acne vulgaris? Clinical and antimicrobial results of a topical combination product containing 1% clindamycin and 5% benzoyl peroxide. Introduction.	2001 Feb	11236213
Synthesis, high-performance liquid chromatography-nuclear magnetic resonance characterization and pharmacokinetics in mice of CD271 glucuronide.	2001 Jun 5	11419733
A comparative trial of two retinoids commonly used in the treatment of acne vulgaris.	2001 Sep	12243706
Developments in topical retinoid therapy for acne.	2001 Sep	11594670
Retinoids--which dermatological indications will benefit in the near future?	2001 Sep-Oct	11586072
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
Efficacy and cutaneous safety of adapalene in black patients versus white patients with acne vulgaris.	2002 Oct	12403317
Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial.	2003 Jul	12833014
Clinical review: topical retinoids.	2003 Oct	14619325
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
Adapalene: a review of its use in the treatment of acne vulgaris.	2004	15212561
Topical tretinoin or adapalene in acne vulgaris: an overview.	2004 Jul	15764031
Facial tolerability of topical retinoid therapy.	2004 Nov-Dec	15624747
Comparison of topical retinoids in the treatment of acne.	2004 Sep-Oct	15556727
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
Acne vulgaris.	2005 Jun	16135322
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
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
The potential risks of nanomaterials: a review carried out for ECETOC.	2006 Aug 14	16907977
The results of the MORE trial: overview.	2006 Jul	16910025

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 17:35:49 UTC 2022` Edited by `admin` on `Fri Dec 16 17:35:49 UTC 2022`
Record UNII	1L4806J2QF
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ADAPALENE

Official Name

English

CD-271

Code

English

IDP-126 Component Adapalene

Code

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 [WHO-DD]

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