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Identification
NameAdapalene
Accession NumberDB00210  (APRD00780)
Typesmall molecule
Groupsapproved
Description

Adapalene is a topical retinoid primarily used in the treatment of acne and is also used (off-label) to treat keratosis pilaris as well as other skin conditions. It is currently marketed by Galderma under the trade names Differin in some countries, and Adaferin in India. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
AdapalenoSpanishINN
AdapalenumLatinINN
SaltsNot Available
Brand names
NameCompany
AdaferinNot Available
DifferinNot Available
Brand mixturesNot Available
Categories
CAS number106685-40-9
WeightAverage: 412.5201
Monoisotopic: 412.203844762
Chemical FormulaC28H28O3
InChI KeyLZCDAPDGXCYOEH-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassPrenol Lipids
SubclassRetinoids
Direct parentRetinoids
Alternative parentsPhenylnaphthalenes; Stilbenes; Naphthalenecarboxylic Acids; Benzoic Acids; Benzoyl Derivatives; Anisoles; Alkyl Aryl Ethers; Carboxylic Acids; Polyamines; Enolates
Substituentsphenylnaphthalene; stilbene; 2-naphthalenecarboxylic acid or derivative; 2-naphthalenecarboxylic acid; acene; naphthalene; benzoic acid; benzoic acid or derivative; anisole; phenol ether; benzoyl; alkyl aryl ether; benzene; carboxylic acid; carboxylic acid derivative; ether; enolate; polyamine
Classification descriptionThis compound belongs to the retinoids. These are compounds that are related to vitamin A, especially retinol.
Pharmacology
IndicationFor the topical treatment of comedo, papular and pustular acne (acne vulgaris) of the face, chest or back.
PharmacodynamicsAdapalene is a chemically stable retinoid-like compound. 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.
Mechanism of actionMechanistically, adapalene binds to specific retinoic acid nuclear receptors (gamma and beta) and retinoid X 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 may normalize the differentiation of follicular epithelial cells resulting in decreased microcomedone formation.
AbsorptionAbsorption of adapalene through human skin is low. Only trace amounts (<0.25 ng/mL) of parent substance have been found in the plasma of acne patients following chronic topical application of adapalene in controlled clinical trials
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Metabolized mainly by O-demethylation, hydroxylation and conjugation, and excretion is primarily by the biliary route.

Route of eliminationExcretion appears to be primarily by the biliary route.
Half lifeNot Available
ClearanceNot Available
ToxicityThe acute oral toxicity of adapalene in mice and rats is greater than 10 mL/kg. Chronic ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.7061
Caco-2 permeable + 0.8439
P-glycoprotein substrate Non-substrate 0.5408
P-glycoprotein inhibitor I Non-inhibitor 0.8074
P-glycoprotein inhibitor II Inhibitor 0.5
Renal organic cation transporter Non-inhibitor 0.8646
CYP450 2C9 substrate Non-substrate 0.7171
CYP450 2D6 substrate Non-substrate 0.8925
CYP450 3A4 substrate Non-substrate 0.5116
CYP450 1A2 substrate Non-inhibitor 0.7812
CYP450 2C9 substrate Inhibitor 0.7758
CYP450 2D6 substrate Non-inhibitor 0.9466
CYP450 2C19 substrate Non-inhibitor 0.653
CYP450 3A4 substrate Non-inhibitor 0.8246
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8509
Ames test Non AMES toxic 0.8575
Carcinogenicity Non-carcinogens 0.8707
Biodegradation Not ready biodegradable 0.9715
Rat acute toxicity 2.6913 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9774
hERG inhibition (predictor II) Non-inhibitor 0.8855
Pharmacoeconomics
Manufacturers
  • Nycomed us inc
  • Galderma laboratories lp
  • Glenmark generics inc usa
  • Pliva hrvatska doo
  • Galderma research and development inc
  • Galderma Laboratories
Packagers
Dosage forms
FormRouteStrength
CreamTopical
GelTopical
Prices
Unit descriptionCostUnit
Differin 0.1% Cream 45 gm Tube227.13USDtube
Differin 0.1% Gel 45 gm Tube227.13USDtube
Differin 0.3% Gel 45 gm Tube219.65USDtube
Differin 0.1% cream4.85USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States75793772005-02-232025-02-23
United States47177201993-05-312010-05-31
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilityPractically InsolubleNot Available
logP8.6Not Available
Predicted Properties
PropertyValueSource
water solubility4.01e-06 g/lALOGPS
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 area46.53ChemAxon
rotatable bond count4ChemAxon
refractivity122.07ChemAxon
polarizability47.65ChemAxon
number of rings6ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
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 Reference
  1. Rolewski SL: Clinical review: topical retinoids. Dermatol Nurs. 2003 Oct;15(5):447-50, 459-65. Pubmed
External Links
ResourceLink
KEGG DrugD01112
PubChem Compound60164
PubChem Substance46505019
ChemSpider54244
ChEBI31174
ChEMBLCHEMBL1265
Therapeutic Targets DatabaseDAP000115
PharmGKBPA448047
Drug Product Database2231592
RxListhttp://www.rxlist.com/cgi/generic3/adapalene.htm
Drugs.comhttp://www.drugs.com/cdi/adapalene-cream.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dif1134.shtml
WikipediaAdapalene
ATC CodesD10AD03
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelshow(25.9 KB)
MSDSshow(57.1 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Retinoic acid receptor gamma

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Retinoic acid receptor gamma P13631 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

2. Retinoic acid receptor beta

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Retinoic acid receptor beta P10826 Details

References:

  1. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. Pubmed
  2. Shroot B, Michel S, Allec J, Chatelus A, Wagner N: A new concept of drug delivery for acne. Dermatology. 1998;196(1):165-70. Pubmed
  3. Michel S, Jomard A, Demarchez M: Pharmacology of adapalene. Br J Dermatol. 1998 Oct;139 Suppl 52:3-7. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Retinoic acid receptor RXR-gamma

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Retinoic acid receptor RXR-gamma P48443 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. 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

4. Retinoic acid receptor RXR-beta

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Retinoic acid receptor RXR-beta P28702 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. 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

5. Retinoic acid receptor alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Retinoic acid receptor alpha P10276 Details

References:

  1. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. Pubmed
  2. Griffiths CE, Ancian P, Humphries J, Poncet M, Rizova E, Michel S, Clucas A: Adapalene 0.1% gel and adapalene 0.1% cream stimulate retinoic acid receptor mediated gene transcription without significant irritative effects in the skin of healthy human volunteers. Br J Dermatol. 1998 Oct;139 Suppl 52:12-6. Pubmed
  3. Michel S, Jomard A, Demarchez M: Pharmacology of adapalene. Br J Dermatol. 1998 Oct;139 Suppl 52:3-7. Pubmed
  4. Shroot B, Michel S, Allec J, Chatelus A, Wagner N: A new concept of drug delivery for acne. Dermatology. 1998;196(1):165-70. Pubmed
  5. 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

6. Retinoic acid receptor RXR-alpha

Kind: protein

Organism: Human

Pharmacological action: no

Actions: other/unknown

Components

Name UniProt ID Details
Retinoic acid receptor RXR-alpha P19793 Details

References:

  1. Bernard BA: Adapalene, a new chemical entity with retinoid activity. Skin Pharmacol. 1993;6 Suppl 1:61-9. Pubmed
  2. 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

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Drug created on June 13, 2005 07:24 / Updated on September 25, 2013 12:36