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Identification
NameAcitretin
Accession NumberDB00459  (APRD00778)
Typesmall molecule
Groupsapproved
Description

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]

Structure
Thumb
Synonyms
SynonymLanguageCode
AcetretinNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
NeotigasonNot Available
SoriataneNot Available
Brand mixturesNot Available
Categories
CAS number55079-83-9
WeightAverage: 326.4293
Monoisotopic: 326.188194698
Chemical FormulaC21H26O3
InChI KeyInChIKey=IHUNBGSDBOWDMA-AQFIFDHZSA-N
InChI
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+
IUPAC Name
(2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid
SMILES
COC1=C(C)C(C)=C(\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O)C(C)=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassPrenol Lipids
SubclassRetinoids
Direct parentRetinoids
Alternative parentsSesquiterpenes; Carbocyclic Fatty Acids; Styrenes; Anisoles; Toluenes; Branched Fatty Acids; Alkyl Aryl Ethers; Unsaturated Fatty Acids; Enones; Carboxylic Acids; Polyamines; Enolates
Substituentscyclofarsesane sesquiterpene; phenol ether; styrene; anisole; alkyl aryl ether; toluene; benzene; enone; polyamine; carboxylic acid; carboxylic acid derivative; ether; enolate
Classification descriptionThis compound belongs to the retinoids. These are compounds that are related to vitamin A, especially retinol.
Pharmacology
IndicationFor the treatment of severe psoriasis in adults.
PharmacodynamicsAcitretin is a retinoid. Retinoids have a structure similar to vitamin A and are involved in the normal growth of skin cells. Acitretin works by inhibiting the excessive cell growth and keratinisation (process by which skin cells become thickened due to the deposition of a protein within them) seen in psoriasis. It therefore reduces the thickening of the skin, plaque formation and scaling.
Mechanism of actionThe 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.
AbsorptionOral absorption of acitretin is optimal when given with food, and is linear and proportional with increasing doses from 25 to 100 mg. Approximately 72% (range 47% to 109%) of the administered dose was absorbed after a single 50 mg dose of acitretin was given to 12 healthy subjects.
Volume of distributionNot Available
Protein bindingOver 99.9% bound to plasma proteins, primarily albumin.
Metabolism

Following oral absorption, acitretin undergoes extensive metabolism and interconversion by simple isomerization to its 13-cis form (cis-acitretin). Both parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates, which are excreted.

Route of eliminationBoth parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates, which are excreted. The chain-shortened metabolites and conjugates of acitretin and cis-acitretin are ultimately excreted in the feces (34% to 54%) and urine (16% to 53%).
Half life49 hours (range 33 to 96 hours)
ClearanceNot Available
ToxicityOral, rat: LD50 = >4000 mg/kg. Symptoms of overdose include headache and vertigo.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Apolipoprotein E
Gene symbol: APOE
UniProt: P02649
rs429358 Not AvailableC allelePsoriasis16433808
Apolipoprotein E
Gene symbol: APOE
UniProt: P02649
rs7412 Not AvailableC allelePsoriasis16433808
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9885
Blood Brain Barrier - 0.5841
Caco-2 permeable + 0.8628
P-glycoprotein substrate Non-substrate 0.6057
P-glycoprotein inhibitor I Non-inhibitor 0.6973
P-glycoprotein inhibitor II Non-inhibitor 0.9382
Renal organic cation transporter Non-inhibitor 0.8899
CYP450 2C9 substrate Non-substrate 0.7907
CYP450 2D6 substrate Non-substrate 0.8202
CYP450 3A4 substrate Non-substrate 0.5108
CYP450 1A2 substrate Non-inhibitor 0.6804
CYP450 2C9 substrate Non-inhibitor 0.9239
CYP450 2D6 substrate Non-inhibitor 0.9409
CYP450 2C19 substrate Non-inhibitor 0.648
CYP450 3A4 substrate Non-inhibitor 0.8768
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5923
Ames test Non AMES toxic 0.8341
Carcinogenicity Non-carcinogens 0.83
Biodegradation Ready biodegradable 0.714
Rat acute toxicity 1.8804 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9216
hERG inhibition (predictor II) Non-inhibitor 0.9501
Pharmacoeconomics
Manufacturers
  • Stiefel laboratories inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
Prices
Unit descriptionCostUnit
Soriatane 17.5 mg capsule30.21USDcapsule
Soriatane 22.5 mg capsule30.21USDcapsule
Soriatane 25 mg capsule21.71USDcapsule
Soriatane 10 mg capsule13.25USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point228-230 °CPhysProp
water solubility0.0729 mg/LNot Available
logP6.40SANGSTER (1993)
Predicted Properties
PropertyValueSource
water solubility4.78e-04 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 area46.53ChemAxon
rotatable bond count6ChemAxon
refractivity104.17ChemAxon
polarizability38.54ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Yatendra Kumar, “Process for the preparation of acitretin.” U.S. Patent US20040192949, issued September 30, 2004.

US20040192949
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD02754
ChEBI50173
ChEMBLCHEMBL1131
Therapeutic Targets DatabaseDAP000743
PharmGKBPA448039
Drug Product Database2070847
RxListhttp://www.rxlist.com/cgi/generic3/acitretin.htm
Drugs.comhttp://www.drugs.com/cdi/acitretin.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/sor1698.shtml
WikipediaAcitretin
ATC CodesD05BB02
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelshow(530 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
DemeclocyclineIncreased risk of intracranial hypertension
DoxycyclineIncreased risk of intracranial hypertension
MethacyclineIncreased risk of intracranial hypertension
MethotrexateAcitretin/etretinate increases the effect and toxicity of methotrexate
MinocyclineIncreased risk of intracranial hypertension.
NorethindroneAcitretine may cause a loss of contraceptive effect
OxytetracyclineIncreased risk of intracranial hypertension
RolitetracyclineIncreased risk of intracranial hypertension
TetracyclineIncreased risk of intracranial hypertension
Vitamin AAcitretin increases the risk of vitamin A toxicity. Avoid vitamin A supplementation while taking acitretin.
Food InteractionsNot Available

1. Retinoic acid receptor RXR-alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

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

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
  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

2. Retinoic acid receptor alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Retinoic acid receptor alpha P10276 Details

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
  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
  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
  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. Epub 2009 Jan 14. Pubmed

3. 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. 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
  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
  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. Epub 2009 Jan 14. Pubmed

4. 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

5. 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

6. 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. 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

7. Retinol-binding protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Retinol-binding protein 1 P09455 Details

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

1. Cytochrome P450 26A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 26A1 O43174 Details

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. Epub 2009 Nov 24. Pubmed

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Urien S, Claudepierre P, Meyer J, Brandt R, Tillement JP: Comparative binding of etretinate and acitretin to plasma proteins and erythrocytes. Biochem Pharmacol. 1992 Nov 3;44(9):1891-3. Pubmed
  2. Preiss JC, Zouboulis CC, Zeitz M, Duchmann R: [Severe erythrodermic psoriasis in a patient with 22q11 deletion syndrome] Med Klin (Munich). 2005 May 13;100(5):275-8. Pubmed
  3. Carillet V, Morliere P, Maziere JC, Huppe G, Santus R, Dubertret L: In vitro interactions of the aromatic retinoids Ro 10-9359 (etretinate) and Ro 10-1670 (acitretin), its main metabolite, with human serum lipoproteins and albumin. Biochim Biophys Acta. 1990 Nov 12;1055(2):98-101. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10