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Identification
Name Adapalene
Accession Number DB00210 (APRD00780)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Adapaleno [INN-Spanish]
Adapalenum [INN-Latin]
Salts Not Available
Brand names
Name Company
Adaferin
Differin
Brand mixtures Not Available
Categories
  • Dermatologic Agents
CAS number 106685-40-9
Weight Average: 412.5201
Monoisotopic: 412.203844762
Chemical Formula C28H28O3
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Retinoids
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Naphthalenes
  • Acetates
  • Benzoates
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Biphenyl and Derivatives
  • Carboxylic Acids and Derivatives
  • Adamantanes
  • Aromatic compounds
  • Anisoles
  • Benzoyl Derivatives
  • Retinoids
  • Cyclooctane and Derivatives
  • Phenyl Esters
Pharmacology
Indication For the topical treatment of comedo, papular and pustular acne (acne vulgaris) of the face, chest or back.
Pharmacodynamics Adapalene 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 action Mechanistically, 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.
Absorption Absorption 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 distribution Not Available
Protein binding Not Available
Metabolism Metabolized mainly by O-demethylation, hydroxylation and conjugation, and excretion is primarily by the biliary route.
Route of elimination Excretion appears to be primarily by the biliary route.
Half life Not Available
Clearance Not Available
Toxicity The 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
Pathways Not Available
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
Form Route Strength
Cream Topical
Gel Topical
Prices
Unit description Cost Unit
Differin 0.1% Cream 45 gm Tube 227.13 USD tube
Differin 0.1% Gel 45 gm Tube 227.13 USD tube
Differin 0.3% Gel 45 gm Tube 219.65 USD tube
Differin 0.1% cream 4.85 USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 7579377 2005-02-23 2025-02-23
United States 4717720 1993-05-31 2010-05-31
Properties
State solid
Experimental Properties
Property Value Source
water solubility Practically Insoluble Not Available
logP 8.6 Not Available
Predicted Properties
Property Value Source
water solubility 4.01e-06 g/l ALOGPS
logP 6.06 ALOGPS
logP 6.46 ChemAxon
logS -8 ALOGPS
pKa (strongest acidic) 3.99 ChemAxon
pKa (strongest basic) -4.8 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 46.53 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 122.07 ChemAxon
polarizability 47.65 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Rolewski SL: Clinical review: topical retinoids. Dermatol Nurs. 2003 Oct;15(5):447-50, 459-65. Pubmed
External Links
Resource Link
KEGG Drug D01112 Link_out
PubChem Compound 60164 Link_out
PubChem Substance 46505019 Link_out
ChemSpider 54244 Link_out
ChEBI 31174 Link_out
ChEMBL 31174 Link_out
Therapeutic Targets Database DAP000115 Link_out
PharmGKB PA448047 Link_out
Drug Product Database 2231592 Link_out
RxList http://www.rxlist.com/cgi/generic3/adapalene.htm Link_out
Drugs.com http://www.drugs.com/cdi/adapalene-cream.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dif1134.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Adapalene Link_out
ATC Codes
  • D10AD03
AHFS Codes
  • 84:92.00
PDB Entries Not Available
FDA label show (25.9 KB)
MSDS show (57.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Retinoic acid receptor gamma-1

Pharmacological action: yes
Actions: agonist

This is a receptor for retinoic acid. This metabolite has profound effects on vertebrate development. Retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression

Organism class: human
UniProt ID: P13631 Link_out
Gene: RARG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

This is a receptor for retinoic acid. This metabolite has profound effects on vertebrate development. Retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression

Organism class: human
UniProt ID: P10826 Link_out
Gene: RARB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA)

Organism class: human
UniProt ID: P48443 Link_out
Gene: RXRG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA)

Organism class: human
UniProt ID: P28702 Link_out
Gene: RXRB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: agonist

This is a receptor for retinoic acid. This metabolite has profound effects on vertebrate development. Retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression

Organism class: human
UniProt ID: P10276 Link_out
Gene: RARA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: no
Actions: other/unknown

Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA). ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer

Organism class: human
UniProt ID: P19793 Link_out
Gene: RXRA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19