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Record Information
Version2.0
Creation Date2014-09-11 02:04:16 UTC
Update Date2014-12-24 20:26:54 UTC
Accession NumberT3D4673
Identification
Common NameAdapalene
ClassSmall Molecule
DescriptionAdapalene 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.
Compound Type
  • Anti-Inflammatory Agent, Non-Steroidal
  • Dermatologic Agent
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
6-(3-(1-Adamantyl)-4-methoxyphenyl)-2-naphthoic acid
Adaferin
Adapaleno
Adapalenum
Differin
Differine
Chemical FormulaC28H28O3
Average Molecular Mass412.520 g/mol
Monoisotopic Mass412.204 g/mol
CAS Registry Number106685-40-9
IUPAC Name6-[3-(adamantan-1-yl)-4-methoxyphenyl]naphthalene-2-carboxylic acid
Traditional Namedifferin
SMILESCOC1=C(C=C(C=C1)C1=CC=C2C=C(C=CC2=C1)C(O)=O)C12CC3CC(CC(C3)C1)C2
InChI IdentifierInChI=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)
InChI KeyInChIKey=LZCDAPDGXCYOEH-UHFFFAOYSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassRetinoids
Direct ParentRetinoids
Alternative Parents
Substituents
  • Adapalene
  • Phenylnaphthalene
  • 2-naphthalenecarboxylic acid
  • 2-naphthalenecarboxylic acid or derivatives
  • Naphthalene
  • Phenoxy compound
  • Anisole
  • Methoxybenzene
  • Phenol ether
  • Alkyl aryl ether
  • Monocyclic benzene moiety
  • Benzenoid
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Organic oxide
  • Organooxygen compound
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility4.01e-06 g/L
LogP8.6
Predicted Properties
PropertyValueSource
Water Solubility4.0e-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 Area46.53 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity122.07 m³·mol⁻¹ChemAxon
Polarizability47.65 ųChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0002-0009000000-2169879160d27fbd36e2JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00xs-8006900000-dedd288878501d101021JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03dj-0009500000-35bff807860c9c78b28cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kb-0119100000-2a0a0656abf4155b2552JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uei-0309000000-7b9438a46b2f18cdc7dfJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0005900000-f70dd1ca3170a3828c5bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0i00-0019300000-00ba903e8fb2abb8a386JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ue9-1149000000-d93742cdc7563deb95faJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0009400000-dc3263730bd61e4428caJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0009000000-981559d240019f5c2b78JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-114r-0229100000-28732127a9e20d3c667aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0007900000-9ec13495747ce0352fb2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03dj-0409700000-93449856a5a1558c8801JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-0693100000-58ea252b7486c8e5f288JSpectraViewer
Toxicity Profile
Route of ExposureAbsorption 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
Mechanism of ToxicityMechanistically, 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.
MetabolismMetabolized 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.
Toxicity ValuesThe acute oral toxicity of adapalene in mice and rats is greater than 10 mL/kg
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the topical treatment of comedo, papular and pustular acne (acne vulgaris) of the face, chest or back.
Minimum Risk LevelNot Available
Health EffectsChronic ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00210
HMDB IDHMDB14355
PubChem Compound ID60164
ChEMBL IDCHEMBL1265
ChemSpider ID54244
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID31174
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAdapalene
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.

MSDSLink
General References
  1. Rolewski SL: Clinical review: topical retinoids. Dermatol Nurs. 2003 Oct;15(5):447-50, 459-65. [14619325 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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 expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.
Gene Name:
RARA
Uniprot ID:
P10276
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. [9204085 ]
  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. [9990415 ]
  3. Michel S, Jomard A, Demarchez M: Pharmacology of adapalene. Br J Dermatol. 1998 Oct;139 Suppl 52:3-7. [9990413 ]
  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. [9557255 ]
  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. [10651997 ]
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 expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.
Gene Name:
RARB
Uniprot ID:
P10826
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. [9204085 ]
  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. [9557255 ]
  3. Michel S, Jomard A, Demarchez M: Pharmacology of adapalene. Br J Dermatol. 1998 Oct;139 Suppl 52:3-7. [9990413 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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 expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Specifically binds 9-cis retinoic acid (9C-RA).
Gene Name:
RXRB
Uniprot ID:
P28702
Molecular Weight:
56921.38 Da
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. [17139284 ]
  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. [17016423 ]
  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. [10651997 ]
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 expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity).
Gene Name:
RXRG
Uniprot ID:
P48443
Molecular Weight:
50870.72 Da
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. [17139284 ]
  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. [17016423 ]
  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. [10651997 ]
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 expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).
Gene Name:
RARG
Uniprot ID:
P13631
Molecular Weight:
50341.405 Da
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. [17139284 ]
  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. [17016423 ]
  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. [10592235 ]
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 expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.
Gene Name:
RXRA
Uniprot ID:
P19793
Molecular Weight:
50810.835 Da
References
  1. Bernard BA: Adapalene, a new chemical entity with retinoid activity. Skin Pharmacol. 1993;6 Suppl 1:61-9. [8142113 ]
  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. [10651997 ]