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Record Information
Version4.0
Creation Date2012-09-06 15:16:49 UTC
Update Date2017-09-27 08:27:37 UTC
HMDB IDHMDB0014602
Secondary Accession Numbers
  • HMDB14602
Metabolite Identification
Common NameAcitretin
DescriptionAcitretin is only found in individuals that have used or taken this drug. It is an oral retinoid effective in the treatment of psoriasis. It is the major metabolite of etretinate with the advantage of a much shorter half-life when compared with etretinate. [PubChem]The mechanism of action of acitretin is unknown, however it is believed to work by targeting specific receptors (retinoid receptors such as RXR and RAR) in the skin which help normalize the growth cycle of skin cells.
Structure
Thumb
Synonyms
ValueSource
(all-e)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acidChEBI
AcitretinaChEBI
AcitretineChEBI
AcitretinumChEBI
all-trans-3,7-Dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-2,4,6,8-nonatetraenoic acidChEBI
EtretinChEBI
NeotigasonChEBI
SoriataneChEBI
(all-e)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoateGenerator
all-trans-3,7-Dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-2,4,6,8-nonatetraenoateGenerator
AcetretinHMDB
IsoetretinMeSH
13-cis-AcitretinMeSH
Acitretin andreu brandMeSH
Acitretin roche brandMeSH
Hoffmann la roche brand OF acitretinMeSH
Hoffmann-la roche brand OF acitretinMeSH
IsoacitretinMeSH
Acitretin, (Z,e,e,e)-isomerMeSH
Andreu brand OF acitretinMeSH
Roche brand OF acitretinMeSH
Chemical FormulaC21H26O3
Average Molecular Weight326.4293
Monoisotopic Molecular Weight326.188194698
IUPAC Name(2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid
Traditional Nameacitretin
CAS Registry Number55079-83-9
SMILES
COC1=C(C)C(C)=C(\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O)C(C)=C1
InChI Identifier
InChI=1S/C21H26O3/c1-14(8-7-9-15(2)12-21(22)23)10-11-19-16(3)13-20(24-6)18(5)17(19)4/h7-13H,1-6H3,(H,22,23)/b9-7+,11-10+,14-8+,15-12+
InChI KeyIHUNBGSDBOWDMA-AQFIFDHZSA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassRetinoids
Direct ParentRetinoids
Alternative Parents
Substituents
  • Retinoic acid
  • Retinoid skeleton
  • Sesquiterpenoid
  • Cyclofarsesane sesquiterpenoid
  • Phenoxy compound
  • Anisole
  • Methoxybenzene
  • Phenol ether
  • Medium-chain fatty acid
  • Styrene
  • Alkyl aryl ether
  • Branched fatty acid
  • Methyl-branched fatty acid
  • Monocyclic benzene moiety
  • Fatty acyl
  • Fatty acid
  • Benzenoid
  • Unsaturated fatty acid
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carbonyl group
  • Organooxygen compound
  • Organic oxide
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Source:

Route of exposure:

  Enteral:

Role

Industrial application:

  Pharmaceutical industry:

Biological role:

Process

Naturally occurring process:

  Biological process:

    Cellular process:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point228 - 230 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.00048 g/LNot Available
LogP5.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00048 g/LALOGPS
logP5.2ALOGPS
logP5.59ChemAxon
logS-5.8ALOGPS
pKa (Strongest Acidic)5.01ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity104.17 m³·mol⁻¹ChemAxon
Polarizability38.54 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-03di-1279000000-d74bbc0348cfdb3b3732View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-001i-4139000000-85e857f30a345651bb66View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-01t9-0592000000-92a48c620c961fdb430fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-056r-1943000000-77c18bcac662a9f6bdcbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-056r-2942000000-57cdf186555912258599View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-05r0-0389000000-28f8ff224c8fd7ac1606View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-02t9-0690000000-11440b22373ebd567609View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-114j-4920000000-bf257c11adfb644686f4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0059000000-2338c505b394d676d7a4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0059-0097000000-d73443e0cee4f07fd0d9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-066r-3391000000-8adb8a7f90aecb16b198View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
NameSMPDB/PathwhizKEGG
No entries found
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00459 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00459 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00459
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4447573
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkAcitretin
METLIN IDNot Available
PubChem Compound5284513
PDB IDNot Available
ChEBI ID50173
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9. [PubMed:11413487 ]
  2. Watson AD: Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res. 2006 Oct;47(10):2101-11. Epub 2006 Aug 10. [PubMed:16902246 ]
  3. Sethi JK, Vidal-Puig AJ: Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. 2007 Jun;48(6):1253-62. Epub 2007 Mar 20. [PubMed:17374880 ]
  4. Lingwood D, Simons K: Lipid rafts as a membrane-organizing principle. Science. 2010 Jan 1;327(5961):46-50. doi: 10.1126/science.1174621. [PubMed:20044567 ]
  5. Gunstone, Frank D., John L. Harwood, and Albert J. Dijkstra (2007). The lipid handbook with CD-ROM. CRC Press.

Enzymes

General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
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
Gene Name:
RARG
Uniprot ID:
P13631
Molecular weight:
50341.4
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: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. [PubMed: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. [PubMed:10592235 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
This is a receptor for retinoic acid. Retinoic acid has profound effects on vertebrate development, is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression. Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing MLL5. Mediates retinoic acid-induced granulopoiesis
Gene Name:
RARA
Uniprot ID:
P10276
Molecular weight:
50770.8
References
  1. Saurat JH: Retinoids and psoriasis: novel issues in retinoid pharmacology and implications for psoriasis treatment. J Am Acad Dermatol. 1999 Sep;41(3 Pt 2):S2-6. [PubMed:10459139 ]
  2. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC: Current use and future potential role of retinoids in dermatology. Drugs. 1997 Mar;53(3):358-88. [PubMed:9074840 ]
  3. Tian K, Norris AW, Lin CL, Li E: The isolation and characterization of purified heterocomplexes of recombinant retinoic acid receptor and retinoid X receptor ligand binding domains. Biochemistry. 1997 May 13;36(19):5669-76. [PubMed:9153406 ]
  4. Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F: Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J. 2009 Jun;23(6):1643-54. doi: 10.1096/fj.08-121392. Epub 2009 Jan 14. [PubMed:19144697 ]
General function:
Involved in monooxygenase activity
Specific function:
Plays a key role in retinoic acid metabolism. Acts on retinoids, including all-trans-retinoic acid (RA) and its stereoisomer 9-cis-RA. Capable of both 4-hydroxylation and 18- hydroxylation. Responsible for generation of several hydroxylated forms of RA, including 4-OH-RA, 4-oxo-RA and 18-OH-RA
Gene Name:
CYP26A1
Uniprot ID:
O43174
Molecular weight:
56198.1
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
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
Gene Name:
RARB
Uniprot ID:
P10826
Molecular weight:
50488.6
References
  1. Berggren Soderlund M, Johannesson G, Fex G: Expression of human all-trans-retinoic acid receptor beta and its ligand-binding domain in Escherichia coli. Biochem J. 1995 May 15;308 ( Pt 1):353-9. [PubMed:7755585 ]
  2. Zouboulis CC: Retinoids--which dermatological indications will benefit in the near future? Skin Pharmacol Appl Skin Physiol. 2001 Sep-Oct;14(5):303-15. [PubMed:11586072 ]
  3. Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F: Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J. 2009 Jun;23(6):1643-54. doi: 10.1096/fj.08-121392. Epub 2009 Jan 14. [PubMed:19144697 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA)
Gene Name:
RXRB
Uniprot ID:
P28702
Molecular weight:
56921.4
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: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. [PubMed:17016423 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA)
Gene Name:
RXRG
Uniprot ID:
P48443
Molecular weight:
50870.7
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: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. [PubMed:17016423 ]
  3. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC: Current use and future potential role of retinoids in dermatology. Drugs. 1997 Mar;53(3):358-88. [PubMed:9074840 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
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
Gene Name:
RXRA
Uniprot ID:
P19793
Molecular weight:
50810.8
References
  1. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC: Current use and future potential role of retinoids in dermatology. Drugs. 1997 Mar;53(3):358-88. [PubMed:9074840 ]
  2. Tian K, Norris AW, Lin CL, Li E: The isolation and characterization of purified heterocomplexes of recombinant retinoic acid receptor and retinoid X receptor ligand binding domains. Biochemistry. 1997 May 13;36(19):5669-76. [PubMed:9153406 ]
General function:
Involved in binding
Specific function:
Intracellular transport of retinol
Gene Name:
RBP1
Uniprot ID:
P09455
Molecular weight:
15850.1
References
  1. Berni R, Clerici M, Malpeli G, Cleris L, Formelli F: Retinoids: in vitro interaction with retinol-binding protein and influence on plasma retinol. FASEB J. 1993 Sep;7(12):1179-84. [PubMed:8375617 ]