Adapalene

Identification

Name
Adapalene
Accession Number
DB00210
Description

Acne vulgaris is a multifactorial disorder of the pilosebaceous unit involving increased sebum production, inflammation, and hyperproliferation/hyperkeratinization of the follicular infundibulum. It is also associated with Cutibacterium acnes (also known as Propionibacterium acnes). Adapalene is a third-generation topical retinoid used for the treatment of acne vulgaris.4 Adapalene has similar efficacy but a superior safety profile compared to tretinoin.5 Tazarotene is more efficacious than adapalene but is designated as pregnancy category X and hence is contraindicated in pregnant women.4 Adapalene can also be combined with benzoyl peroxide (BPO), which possesses bactericidal properties6, and either adapalene alone, or adapalene BPO combination products, are commonly used to treat mild-to-severe acne.4

Differin®, produced by Galderma Labs, was first granted FDA approval on May 31st, 1996, as a 0.1% adapalene topical solution. Differin was later made available as 0.1% gel, cream, or lotion, or 0.3% gel products. On December 8th, 2008, Galderma Labs gained FDA approval for Epiduo®, a 0.1% adapalene, 2.5% BPO combination gel.8

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 412.5201
Monoisotopic: 412.203844762
Chemical Formula
C28H28O3
Synonyms
  • 6-(3-(1-Adamantyl)-4-methoxyphenyl)-2-naphthoic acid
  • Adapalene
  • Adapalène
  • Adapaleno
  • Adapalenum
External IDs
  • CD 271
  • CD-271

Pharmacology

Indication

Adapalene is indicated for the topical treatment of acne vulgaris in patients aged 12 and over.8

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Adapalene is anticomedogenic, preventing the formation of new comedones and inflammatory lesions, and also acts to reduce inflammation by modulating the innate immune response.2 Like other retinoid compounds, adapalene is chemically stable but photosensitive; use with sunscreen is recommended. Minor skin irritations, including erythema, scaling, dryness, and stinging/burning, have been reported.8

Mechanism of action

Adapalene is used for the treatment/maintenance of mild-to-severe acne (acne vulgaris). Acne is a multifactorial condition, and evidence exists to support multiple mechanisms of action for adapalene. Adapalene binds to retinoic acid receptor (RAR)-beta and RAR-gamma; this complex subsequently binds to one of three retinoid X receptors (RXRs), which as a complex is capable of binding DNA to modulate transcriptional activity.1 Although the full extent of transcriptional modulation is not described, retinoid activation is generally known to affect cellular proliferation and differentiation7, and adapalene has been shown to inhibit HeLa cell proliferation and human keratinocyte differentiation.3 These effects primarily account for adapalene's comedolytic and anticomedogenic properties.

In addition, adapalene modulates the immune response by down-regulating toll-like receptor 2 (TLR-2) expression and inhibiting the transcription factor activator protein 1 (AP-1). TLR-2 recognizes Cutibacterium acnes (formerly Propionibacterium acnes), the bacterium primarily associated with acne. TLR-2 activation causes nuclear translocation of AP-1 and downstream pro-inflammatory gene regulation. Therefore, adapalene has a general anti-inflammatory effect, which reduces inflammation-mediated acne symptoms.2

When used with benzoyl peroxide, which possesses free radical-mediated bactericidal effects, the combination acts synergistically to reduced comedones and inflammatory lesions.2

TargetActionsOrganism
ARetinoic acid receptor beta
agonist
Humans
ARetinoic acid receptor gamma
agonist
Humans
ARetinoic acid receptor RXR-beta
agonist
Humans
ARetinoic acid receptor RXR-gamma
agonist
Humans
ARetinoic acid receptor RXR-alpha
agonist
Humans
ATranscription factor AP-1
antagonist
Humans
AToll-like receptor 2
antagonist
Humans
URetinoic acid receptor alphaNot AvailableHumans
UAspartate aminotransferase, cytoplasmic
inhibitor
Humans
Absorption

Adapalene is applied topically and absorbed through the skin. In one clinical study treating patients once per day with 2g of 0.3% gel applied to 2 mg/cm2 of skin, 15 patients had detectable blood plasma adapalene levels (0.1 ng/ml) resulting in a mean Cmax of 0.553 ± 0.466 ng/ml and a mean AUC of 8.37 ± 8.46 ng*h/ml on day 10.8

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Extensive information regarding adapalene metabolism in humans is unavailable, although it is known to accumulate in the liver and GI-tract. In human, mouse, rat, rabbit, and dog cultured hepatocytes, metabolism appears to affect the methoxybenzene moiety but remains incompletely characterized. The major products of metabolism are glucuronides. Approximately 25% of the drug is metabolized; the rest is excreted as parent drug.9

Route of elimination

Adapalene is primarily excreted by the biliary route at about 30 ng/g of the topically applied amount. Approximately 75% of the drug remains unchanged.1

Half-life

In one clinical study, after ten days of treatment with 2g of 0.3% cream or gel, the terminal half-life was between 7 and 51 hours, with a mean of 17.2 ± 10.2.8

Clearance

Adapalene is rapidly cleared from blood plasma, typically undetectable after 72 hours following topical application.8

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Toxicity information regarding adapalene is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as redness, scaling, and skin discomfort. Symptomatic and supportive measures are recommended.8

Adapalene has an acute oral LD50 in S-D rats and CD-1 mice of over 5000 mg/kg. The LD50 of 0.3% applied topically to Credo OF1 mice is over 10 ml/kg (30 mg/kg). No systemic or local toxicity was observed in rats treated topically with 6 mg/kg/day of 0.3% adapalene.9

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
ResorcinolThe risk or severity of adverse effects can be increased when Resorcinol is combined with Adapalene.
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Adapalene.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

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Food Interactions
No interactions found.

Products

International/Other Brands
Adaferin / Differine
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdapaleneCream0.1 g/100gTopicalPerrigo New York Inc.2010-10-26Not applicableUS flag
DifferinSolution1 mg/1mLTopicalDPT Laboratories, Ltd.1998-01-282006-01-31US flag
DifferinGel0.1 %TopicalGalderma1996-12-31Not applicableCanada flag
DifferinLotion1 mg/1gTopicalPhysicians Total Care, Inc.2010-04-27Not applicableUS flag
DifferinLotion0.1 g/100mLTopicalGalderma2010-03-31Not applicableUS flag
DifferinLiquid0.1 %TopicalGalderma2001-08-082003-07-08Canada flag
DifferinGel1 mg/1gTopicalPhysicians Total Care, Inc.2004-07-07Not applicableUS flag
DifferinGel1 mg/1gTopicalGalderma Laboratories, L.P.1996-05-312019-07-08US flag
DifferinCream1 mg/1gTopicalPhysicians Total Care, Inc.2005-04-19Not applicableUS flag
DifferinGel3 mg/1gTopicalGalderma2009-09-15Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdapaleneGel1 mg/1gTopicalPhysicians Total Care, Inc.2010-07-09Not applicableUS flag
AdapaleneGel1 mg/1gTopicalA-S Medication Solutions2010-07-01Not applicableUS flag
AdapaleneGel3 mg/1gTopicalSandoz Inc.2014-04-28Not applicableUS flag
AdapaleneGel3 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.2016-06-23Not applicableUS flag
AdapaleneSolution1 mg/1mLTopicalAllegis Pharmaceuticals, LLC2018-08-202019-12-31US flag
AdapaleneCream1 mg/1gTopicalE. Fougera & Co. a division of Fougera Pharmaceuticals Inc.2010-06-30Not applicableUS flag
AdapaleneGel3 mg/1gTopicalAleor Dermaceuticals Limited2020-06-26Not applicableUS flag
AdapaleneGel1 mg/1gTopicalTeva Pharmaceuticals USA, Inc.2010-06-02Not applicableUS flag
AdapaleneGel3 mg/1gTopicalOwen Laboratories, Inc.2009-09-152018-03-01US flag
AdapaleneGel45 g/1gTopicalPru Gen Pharmaceuticals2016-03-04Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdapaleneGel1 mg/1gTopicalCardinal Health (Leader) 700002019-02-19Not applicableUS flag
AdapaleneGel1 mg/1gTopicalL’Oreal USA Products Inc2019-09-18Not applicableUS flag
AdapaleneGel1 mg/1gTopicalSafeway, Inc.2019-08-30Not applicableUS flag
AdapaleneGel1 mg/1gTopicalDolgencorp, Inc. (Dollar General & Rexall)2019-11-29Not applicableUS flag
AdapaleneGel1 mg/1gTopicalCVS PHARMACY2019-08-01Not applicableUS flag
AdapaleneGel1 mg/1gTopicalMEIJER, INC.2019-11-29Not applicableUS flag
DifferinGel1 mg/1gTopicalGalderma Laboratories, L.P.2016-07-08Not applicableUS flag
Proactiv MD Adapalene Acne TreatmentGel0.1 g/100gTopicalThe Proactiv Company, Llc2017-03-27Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Adapalene and Benzoyl PeroxideAdapalene (0.1 g/100g) + Benzoyl peroxide (2.5 g/100g)GelTopicalPerrigo New York Inc2018-01-24Not applicableUS flag
ADAPALENE and BENZOYL PEROXIDEAdapalene (1 mg/1g) + Benzoyl peroxide (25 mg/1g)GelTopicalTaro Pharmaceuticals U.S.A., Inc.2018-01-24Not applicableUS flag
Adapalene and Benzoyl PeroxideAdapalene (1 mg/1g) + Benzoyl peroxide (25 mg/1g)GelTopicalGlenmark Pharmaceuticals Inc., USA2019-11-08Not applicableUS flag
Adapalene and Benzoyl PeroxideAdapalene (1 mg/1g) + Benzoyl peroxide (25 mg/1g)GelTopicalActavis Pharma, Inc.2017-07-27Not applicableUS flag
Adapalene and Benzoyl PeroxideAdapalene (3 mg/1g) + Benzoyl peroxide (25 mg/1g)GelTopicalTaro Pharmaceuticals U.S.A., Inc.2018-10-17Not applicableUS flag
Adapalene and Benzoyl PeroxideAdapalene (1 mg/1g) + Benzoyl peroxide (25 mg/1g)GelTopicalPrasco, Laboratories2017-08-03Not applicableUS flag
Adapalene and Benzoyl PeroxideAdapalene (1 mg/1g) + Benzoyl peroxide (25 mg/1g)GelTopicalSandoz Inc.2018-05-23Not applicableUS flag
EpiduoAdapalene (1 mg/1g) + Benzoyl peroxide (25 mg/1g)GelTopicalPhysicians Total Care, Inc.2009-02-24Not applicableUS flag
EpiduoAdapalene (1 mg/1g) + Benzoyl peroxide (25 mg/1g)GelTopicalGalderma2008-12-08Not applicableUS flag
Epiduo ForteAdapalene (3 mg/1g) + Benzoyl peroxide (25 mg/1g)GelTopicalGalderma Laboratories, L.P.2015-07-01Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Adapalene 0.1% / Benzoyl Peroxide 2.5% / Clindamycin 1%Adapalene (0.1 g/100g) + Benzoyl peroxide (2.5 g/100g) + Clindamycin phosphate (1 g/100g)GelTopicalSincerus Florida, LLC2019-05-10Not applicableUS flag
Adapalene 0.1% / Benzoyl Peroxide 2.5% / Niacinamide 4%Adapalene (0.1 g/100g) + Benzoyl peroxide (2.5 g/100g) + Nicotinamide (4 g/100g)GelTopicalSincerus Florida, LLC2019-05-10Not applicableUS flag
Adapalene 0.3% / Benzoyl Peroxide 2.5% / Clindamycin 1%Adapalene (0.3 g/100g) + Benzoyl peroxide (2.5 g/100g) + Clindamycin phosphate (1 g/100g)GelTopicalSincerus Florida, LLC2019-05-01Not applicableUS flag
Adapalene 0.3% / Benzoyl Peroxide 2.5% / Niacinamide 4%Adapalene (0.3 g/100g) + Benzoyl peroxide (2.5 g/100g) + Nicotinamide (4 g/100g)GelTopicalSincerus Florida, LLC2019-05-01Not applicableUS flag
Adapalene 0.3% / Niacinamide 4%Adapalene (0.3 g/100g) + Nicotinamide (4 g/100g)GelTopicalSincerus Florida, LLC2019-05-10Not applicableUS flag
Clindap-TAdapalene (0.15 g/0.15g) + Clindamycin phosphate (0.5 g/0.5g)KitTopicalAccumix Pharmaceuticals2014-12-152015-07-17US flag
NuvyaAdapalene (0.15 g/0.15g) + Diclofenac sodium (1 g/1g) + Tamoxifen citrate (0.1 g/0.1g)KitTopicalAccumix Pharmaceuticals2014-12-152015-07-17US flag

Categories

ATC Codes
D10AD03 — AdapaleneD10AD53 — Adapalene, combinations
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as retinoids. These are oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Retinoids
Direct Parent
Retinoids
Alternative Parents
Phenylnaphthalenes / Naphthalenecarboxylic acids / Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives
Substituents
2-naphthalenecarboxylic acid / 2-naphthalenecarboxylic acid or derivatives / Adapalene / Alkyl aryl ether / Anisole / Aromatic homopolycyclic compound / Benzenoid / Carboxylic acid / Carboxylic acid derivative / Ether
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
monocarboxylic acid, adamantanes (CHEBI:31174)

Chemical Identifiers

UNII
1L4806J2QF
CAS number
106685-40-9
InChI Key
LZCDAPDGXCYOEH-UHFFFAOYSA-N
InChI
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)
IUPAC Name
6-[3-(adamantan-1-yl)-4-methoxyphenyl]naphthalene-2-carboxylic acid
SMILES
COC1=C(C=C(C=C1)C1=CC2=C(C=C1)C=C(C=C2)C(O)=O)C12CC3CC(CC(C3)C1)C2

References

Synthesis Reference

Graziano Castaldi, Pietro Allegrini, Gabriele Razzetti, Mauro Ercoli, "Process for the preparation of adapalene." U.S. Patent US20060229465, issued October 12, 2006.

US20060229465
General References
  1. Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [PubMed:19929446]
  2. Leyden J: Recent advances in the use of adapalene 0.1%/benzoyl peroxide 2.5% to treat patients with moderate to severe acne. J Dermatolog Treat. 2016;27 Suppl 1:S4-13. doi: 10.3109/09546634.2016.1145338. [PubMed:26947815]
  3. Shroot B: Pharmacodynamics and pharmacokinetics of topical adapalene. J Am Acad Dermatol. 1998 Aug;39(2 Pt 3):S17-24. doi: 10.1016/s0190-9622(98)70440-2. [PubMed:9703119]
  4. Zaenglein AL: Acne Vulgaris. N Engl J Med. 2018 Oct 4;379(14):1343-1352. doi: 10.1056/NEJMcp1702493. [PubMed:30281982]
  5. Grosshans E, Marks R, Mascaro JM, Torras H, Meynadier J, Alirezai M, Finlay AY, Soto P, Poncet M, Verschoore M, Clucas A: Evaluation of clinical efficacy and safety of adapalene 0.1% gel versus tretinoin 0.025% gel in the treatment of acne vulgaris, with particular reference to the onset of action and impact on quality of life. Br J Dermatol. 1998 Oct;139 Suppl 52:26-33. doi: 10.1046/j.1365-2133.1998.1390s2026.x. [PubMed:9990418]
  6. Leyden JJ, Wortzman M, Baldwin EK: Antibiotic-resistant Propionibacterium acnes suppressed by a benzoyl peroxide cleanser 6%. Cutis. 2008 Dec;82(6):417-21. [PubMed:19181031]
  7. Beckenbach L, Baron JM, Merk HF, Loffler H, Amann PM: Retinoid treatment of skin diseases. Eur J Dermatol. 2015 Sep-Oct;25(5):384-91. doi: 10.1684/ejd.2015.2544. [PubMed:26069148]
  8. FDA Approved Drug Products: Differin (adapalene) gel [Link]
  9. FDA: Pharmacology/Toxicology Review and Evaluation (adapalene) [Link]
  10. DPD Monograph: Differin (adapalene) topical cream/gel/lotion [Link]
  11. FDA Approved Drug Products: Epiduo (adapalene and benzoyl peroxide), gel [Link]
Human Metabolome Database
HMDB0014355
KEGG Drug
D01112
PubChem Compound
60164
PubChem Substance
46505019
ChemSpider
54244
BindingDB
50048280
RxNav
60223
ChEBI
31174
ChEMBL
CHEMBL1265
ZINC
ZINC000003784182
Therapeutic Targets Database
DAP000115
PharmGKB
PA448047
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Adapalene
AHFS Codes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
FDA label
Download (25.9 KB)
MSDS
Download (57.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableP Acnes Colonization1
4CompletedPreventionAcne Vulgaris / Atrophic Acne Scars1
4CompletedSupportive CareAcne1
4CompletedTreatmentAcne3
4CompletedTreatmentAcne Vulgaris26
4Not Yet RecruitingTreatmentAcne1
4Not Yet RecruitingTreatmentAcne Vulgaris1
4RecruitingTreatmentAcne Vulgaris1
4TerminatedTreatmentAcne Vulgaris1
3CompletedTreatmentAcne5

Pharmacoeconomics

Manufacturers
  • Nycomed us inc
  • Galderma laboratories lp
  • Glenmark generics inc usa
  • Pliva hrvatska doo
  • Galderma research and development inc
  • Galderma Laboratories
Packagers
  • Ameri-Pac Inc.
  • DPT Laboratories Ltd.
  • E. Fougera and Co.
  • Galderma Laboratories
  • Glenmark Generics Ltd.
  • Lake Erie Medical and Surgical Supply
  • Physicians Total Care Inc.
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
CreamTopical0.1 g/100g
CreamTopical1 mg/1g
GelTopical1 mg/1g
GelTopical45 g/1g
LotionTopical.1 g/100mL
SwabTopical1 mg/1mL
GelTopical1 g
KitTopical
Gel
Cream0.1 %
Cream100 mg/100g
CreamTopical0.1 %
Gel0.1 %
Gel100 mg/100g
GelTopical3 mg/1g
LiquidTopical0.1 %
LotionTopical0.1 g/100mL
LotionTopical0.1 %
LotionTopical1 mg/1g
SolutionTopical1 mg/1mL
Cream
GelTopical0.1 g
GelTopical
GelTopical
GelTopical0.3 %
GelTopical0.3 g
SolutionTopical0.1 g
GelTopical0.1 %
GelTopical0.1 g/100g
CreamTopical0.1 g
Prices
Unit descriptionCostUnit
Differin 0.1% Cream 45 gm Tube227.13USD tube
Differin 0.1% Gel 45 gm Tube227.13USD tube
Differin 0.3% Gel 45 gm Tube219.65USD tube
Differin 0.1% cream4.85USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US4717720No1988-01-052010-05-31US flag
US8909305No2014-12-092022-12-23US flag
US7579377No2009-08-252025-02-23US flag
US7834060No2010-11-162023-03-12US flag
US7868044No2011-01-112023-03-12US flag
US8703820No2014-04-222023-03-12US flag
US7838558No2010-11-232023-03-12US flag
US7737181No2010-06-152024-08-29US flag
US7964202No2011-06-212024-09-01US flag
US8071644No2011-12-062027-07-18US flag
US8080537No2011-12-202027-07-18US flag
US8105618No2012-01-312022-12-23US flag
US8129362No2012-03-062027-07-18US flag
US8445543No2013-05-212027-07-12US flag
US8809305No2014-08-192022-12-23US flag
US8936800No2015-01-202022-12-23US flag
US8241649No2012-08-142022-12-23US flag
US7820186No2010-10-262025-11-23US flag
US7998467No2011-08-162028-05-31US flag
US8435502No2013-05-072026-09-15US flag
US8709392No2014-04-292026-09-15US flag
US8785420No2014-07-222022-12-23US flag
US8729127No2014-05-202023-03-12US flag
US9381179No2016-07-052023-03-12US flag
US9387187No2016-07-122023-03-12US flag
US9814690No2017-11-142022-12-23US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)300http://datasheets.scbt.com/sds/aghs/en/sc-203803.pdf
boiling point (°C)606.3http://datasheets.scbt.com/sds/aghs/en/sc-203803.pdf
logP6.917http://www.chemspider.com/Chemical-Structure.54244.html?rid=2edd1b0e-994a-4cdc-870c-186c62dcad5a&page_num=0
Predicted Properties
PropertyValueSource
Water Solubility4.01e-06 mg/mLALOGPS
logP6.06ALOGPS
logP6.46ChemAxon
logS-8ALOGPS
pKa (Strongest Acidic)3.99ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity122.07 m3·mol-1ChemAxon
Polarizability47.65 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.7061
Caco-2 permeable+0.8439
P-glycoprotein substrateNon-substrate0.5408
P-glycoprotein inhibitor INon-inhibitor0.8074
P-glycoprotein inhibitor IIInhibitor0.5
Renal organic cation transporterNon-inhibitor0.8646
CYP450 2C9 substrateNon-substrate0.7171
CYP450 2D6 substrateNon-substrate0.8925
CYP450 3A4 substrateNon-substrate0.5116
CYP450 1A2 substrateNon-inhibitor0.7812
CYP450 2C9 inhibitorInhibitor0.7758
CYP450 2D6 inhibitorNon-inhibitor0.9466
CYP450 2C19 inhibitorNon-inhibitor0.653
CYP450 3A4 inhibitorNon-inhibitor0.8246
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8509
Ames testNon AMES toxic0.8575
CarcinogenicityNon-carcinogens0.8707
BiodegradationNot ready biodegradable0.9715
Rat acute toxicity2.6913 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9774
hERG inhibition (predictor II)Non-inhibitor0.8855
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
Curator comments
Adapalene binds preferentially to the retinoic acid receptor (RAR) beta and gamma subtypes; binding to the alpha subtype is minimal.
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARB
Uniprot ID
P10826
Uniprot Name
Retinoic acid receptor beta
Molecular Weight
50488.63 Da
References
  1. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [PubMed:9204085]
  2. Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [PubMed:19929446]
  3. Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [PubMed:31273085]
  4. Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [PubMed:10651997]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
Curator comments
Adapalene binds preferentially to the retinoic acid receptor (RAR) beta and gamma subtypes; binding to the alpha subtype is minimal.
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARG
Uniprot ID
P13631
Uniprot Name
Retinoic acid receptor gamma
Molecular Weight
50341.405 Da
References
  1. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [PubMed:9204085]
  2. Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [PubMed:19929446]
  3. Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [PubMed:31273085]
  4. Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [PubMed:10651997]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
Curator comments
Adapalene binds directly to retinoic acid receptors (RARs); the adapalene-RAR complex forms heterodimers with retinoid X receptors (RXRs, subdivided into alpha, beta, and gamma subtypes), which can bind DNA and modulate transcription.
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRB
Uniprot ID
P28702
Uniprot Name
Retinoic acid receptor RXR-beta
Molecular Weight
56921.38 Da
References
  1. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [PubMed:9204085]
  2. Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [PubMed:19929446]
  3. Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [PubMed:31273085]
  4. Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [PubMed:10651997]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
Curator comments
Adapalene binds directly to retinoic acid receptors (RARs); the adapalene-RAR complex forms heterodimers with retinoid X receptors (RXRs, subdivided into alpha, beta, and gamma subtypes), which can bind DNA and modulate transcription.
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRG
Uniprot ID
P48443
Uniprot Name
Retinoic acid receptor RXR-gamma
Molecular Weight
50870.72 Da
References
  1. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [PubMed:9204085]
  2. Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [PubMed:19929446]
  3. Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [PubMed:31273085]
  4. Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [PubMed:10651997]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
Curator comments
Adapalene binds directly to retinoic acid receptors (RARs); the adapalene-RAR complex forms heterodimers with retinoid X receptors (RXRs, subdivided into alpha, beta, and gamma subtypes), which can bind DNA and modulate transcription.
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRA
Uniprot ID
P19793
Uniprot Name
Retinoic acid receptor RXR-alpha
Molecular Weight
50810.835 Da
References
  1. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [PubMed:9204085]
  2. Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [PubMed:19929446]
  3. Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [PubMed:31273085]
  4. Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [PubMed:10651997]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Curator comments
Adapalene, likely through binding to RARs/RXRs, exerts a transrepressive effect on AP-1 activity.
General Function
Transcriptional activator activity, rna polymerase ii transcription factor binding
Specific Function
Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expre...
Gene Name
JUN
Uniprot ID
P05412
Uniprot Name
Transcription factor AP-1
Molecular Weight
35675.32 Da
References
  1. Leyden J: Recent advances in the use of adapalene 0.1%/benzoyl peroxide 2.5% to treat patients with moderate to severe acne. J Dermatolog Treat. 2016;27 Suppl 1:S4-13. doi: 10.3109/09546634.2016.1145338. [PubMed:26947815]
  2. Lefebvre P, Martin PJ, Flajollet S, Dedieu S, Billaut X, Lefebvre B: Transcriptional activities of retinoic acid receptors. Vitam Horm. 2005;70:199-264. doi: 10.1016/S0083-6729(05)70007-8. [PubMed:15727806]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Curator comments
Adapalene down-regulates TLR-2 expression in a dose-dependent manner.
General Function
Triacyl lipopeptide binding
Specific Function
Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to ...
Gene Name
TLR2
Uniprot ID
O60603
Uniprot Name
Toll-like receptor 2
Molecular Weight
89836.575 Da
References
  1. Tenaud I, Khammari A, Dreno B: In vitro modulation of TLR-2, CD1d and IL-10 by adapalene on normal human skin and acne inflammatory lesions. Exp Dermatol. 2007 Jun;16(6):500-6. doi: 10.1111/j.1600-0625.2007.00552.x. [PubMed:17518990]
  2. Leyden J: Recent advances in the use of adapalene 0.1%/benzoyl peroxide 2.5% to treat patients with moderate to severe acne. J Dermatolog Treat. 2016;27 Suppl 1:S4-13. doi: 10.3109/09546634.2016.1145338. [PubMed:26947815]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Curator comments
Adapalene binds preferentially to the retinoic acid receptor (RAR) beta and gamma subtypes; binding to the alpha subtype is minimal.
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARA
Uniprot ID
P10276
Uniprot Name
Retinoic acid receptor alpha
Molecular Weight
50770.805 Da
References
  1. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [PubMed:9204085]
  2. Pierard GE, Pierard-Franchimont C, Paquet P, Quatresooz P: Spotlight on adapalene. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1565-75. doi: 10.1517/17425250903386269. [PubMed:19929446]
  3. Ghyselinck NB, Duester G: Retinoic acid signaling pathways. Development. 2019 Jul 4;146(13). pii: 146/13/dev167502. doi: 10.1242/dev.167502. [PubMed:31273085]
  4. Kim MJ, Ciletti N, Michel S, Reichert U, Rosenfield RL: The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol. 2000 Feb;114(2):349-53. [PubMed:10651997]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Pyridoxal phosphate binding
Specific Function
Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a sca...
Gene Name
GOT1
Uniprot ID
P17174
Uniprot Name
Aspartate aminotransferase, cytoplasmic
Molecular Weight
46247.14 Da
References
  1. Wang Q, Zhang Q, Luan S, Yang K, Zheng M, Li K, Chen L, Li H: Adapalene inhibits ovarian cancer ES-2 cells growth by targeting glutamic-oxaloacetic transaminase 1. Bioorg Chem. 2019 Dec;93:103315. doi: 10.1016/j.bioorg.2019.103315. Epub 2019 Sep 26. [PubMed:31605927]

Drug created on June 13, 2005 07:24 / Updated on October 26, 2020 22:41

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