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

Molecular Formula	C28H28O3
Molecular Weight	412.5212
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 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

The role of specific retinoid receptors in sebocyte growth and differentiation in culture.	2000 Feb	10651997
Adapalene biochemistry and the evolution of a new topical retinoid for treatment of acne.	2001	11843234
Comparison of the cumulative irritation potential of adapalene gel and cream with that of erythromycin/tretinoin solution and gel and erythromycin/isotretinoin gel.	2001 Feb	11293554
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
Acral Darier's disease successfully treated with adapalene.	2001 Jan-Feb	11411920
Lipid analysis of follicular casts from cyanoacrylate strips as a new method for studying therapeutic effects of antiacne agents.	2001 Jul	11453902
Comparison of treatment of acne vulgaris with alternate-day applications of tazarotene 0.1% gel and once-daily applications of adapalene 0.1% gel: a randomized trial.	2001 Jun	11499327
Synthesis, high-performance liquid chromatography-nuclear magnetic resonance characterization and pharmacokinetics in mice of CD271 glucuronide.	2001 Jun 5	11419733
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
Polarized light photography and videomicroscopy greatly enhance the capability of estimating the therapeuic response to a topical retinoid (adapalene) in acne vulgaris.	2001 Oct	11845945
The modern age of acne therapy: a review of current treatment options.	2001 Sep-Oct	11514915
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
Prospective study of depressive symptoms and quality of life in acne vulgaris patients treated with isotretinoin compared to antibiotic and topical therapy.	2002 Nov	12423432
Topical adapalene gel 0.1% vs. isotretinoin gel 0.05% in the treatment of acne vulgaris: a randomized open-label clinical trial.	2002 Sep	12207595
Current concepts of the pathogenesis of acne: implications for drug treatment.	2003	12887264
Optimizing treatment with topical tazarotene.	2003	12627995
Management of acne.	2003 Jan	12540312
Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial.	2003 Jul	12833014
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
The synthetic retinoid adapalene inhibits proliferation and induces apoptosis in colorectal cancer cells in vitro.	2003 Nov 10	14506747
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
Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: a multicenter, randomized, investigator-blinded study.	2003 Sep	12963897
A review of the use of combination therapies for the treatment of acne vulgaris.	2003 Sep	12963896
Adapalene: a review of its use in the treatment of acne vulgaris.	2004	15212561
A successful maintenance approach in inflammatory acne with adapalene gel 0.1% after an initial treatment in combination with clindamycin topical solution 1% or after monotherapy with clindamycin topical solution 1%.	2004 Dec	15764049
Topical tretinoin or adapalene in acne vulgaris: an overview.	2004 Jul	15764031
Topical agents used in the management of hyperpigmentation.	2004 Jun-Jul	15334278
Drugs. Adapalene.	2005 Apr 26-May 2	15881906
Topical retinoids in inflammatory acne: a retrospective, investigator-blinded, vehicle-controlled, photographic assessment.	2005 Feb	15811485
Fox fordyce disease in a prepubertal girl.	2005 Jan-Feb	15660912
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
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
Mechanism-based treatment of acne vulgaris: the value of combination therapy.	2005 May-Jun	15898282
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

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 Jun 25 21:11:53 UTC 2021` Edited by `admin` on `Fri Jun 25 21:11:53 UTC 2021`
Record UNII	1L4806J2QF
Record Status	`Validated (UNII)`
Record Version

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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