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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
(all-e)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid
Acetretin
Acitretin
Acitretina
Acitretine
Acitretinum
all-trans-3,7-Dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-2,4,6,8-nonatetraenoic acid
Etretin
Neotigason
Soriatane
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Acitretincapsule25 mg/1oralPrasco Laboratories2013-07-19Not applicableUs
Acitretincapsule10 mg/1oralPrasco Laboratories2013-07-19Not applicableUs
Soriatanecapsule10 mg/1oralStiefel Laboratories Inc1996-11-01Not applicableUs
Soriatanecapsule10 mgoralActavis Specialty Pharmaceuticals Co1994-12-31Not applicableCanada
Soriatanecapsule25 mgoralActavis Specialty Pharmaceuticals Co1994-12-31Not applicableCanada
Soriatanecapsule17.5 mg/1oralStiefel Laboratories Inc2010-01-04Not applicableUs
Soriatanecapsule25 mg/1oralStiefel Laboratories Inc1996-11-01Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Acitretincapsule10 mg/1oralTeva Pharmaceuticals USA Inc2013-07-19Not applicableUs
Acitretincapsule25 mg/1oralActavis Pharma, Inc.2016-01-04Not applicableUs
Acitretincapsule22.5 mg/1oralActavis Pharma, Inc.2016-01-04Not applicableUs
Acitretincapsule25 mg/1oralMylan Pharmaceuticals Inc.2016-03-10Not applicableUs
Acitretincapsule17.5 mg/1oralActavis Pharma, Inc.2016-01-04Not applicableUs
Acitretincapsule10 mg/1oralMylan Pharmaceuticals Inc.2016-03-10Not applicableUs
Acitretincapsule10 mg/1oralActavis Pharma, Inc.2016-01-04Not applicableUs
Acitretincapsule25 mg/1oralSigmapharm Laboratories, LLC2015-09-16Not applicableUs
Acitretincapsule17.5 mg/1oralTeva Pharmaceuticals USA Inc2013-07-19Not applicableUs
Acitretincapsule17.5 mg/1oralSigmapharm Laboratories, LLC2015-09-16Not applicableUs
Acitretincapsule25 mg/1oralTeva Pharmaceuticals USA Inc2013-07-19Not applicableUs
Acitretincapsule10 mg/1oralSigmapharm Laboratories, LLC2015-09-16Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
NeotigasonNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIILCH760E9T7
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
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
  • Retinoid skeleton
  • Cyclofarsesane sesquiterpenoid
  • Sesquiterpenoid
  • Carbocyclic fatty acid
  • Medium-chain fatty acid
  • Styrene
  • Phenol ether
  • Anisole
  • Methyl-branched fatty acid
  • Branched fatty acid
  • Alkyl aryl ether
  • Fatty acyl
  • Fatty acid
  • Benzenoid
  • Unsaturated fatty acid
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.9885
Blood Brain Barrier-0.5841
Caco-2 permeable+0.8628
P-glycoprotein substrateNon-substrate0.6057
P-glycoprotein inhibitor INon-inhibitor0.6973
P-glycoprotein inhibitor IINon-inhibitor0.9382
Renal organic cation transporterNon-inhibitor0.8899
CYP450 2C9 substrateNon-substrate0.7907
CYP450 2D6 substrateNon-substrate0.8202
CYP450 3A4 substrateNon-substrate0.5108
CYP450 1A2 substrateNon-inhibitor0.6804
CYP450 2C9 inhibitorNon-inhibitor0.9239
CYP450 2D6 inhibitorNon-inhibitor0.9409
CYP450 2C19 inhibitorNon-inhibitor0.648
CYP450 3A4 inhibitorNon-inhibitor0.8768
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5923
Ames testNon AMES toxic0.8341
CarcinogenicityNon-carcinogens0.83
BiodegradationReady biodegradable0.714
Rat acute toxicity1.8804 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9216
hERG inhibition (predictor II)Non-inhibitor0.9501
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Stiefel laboratories inc
Packagers
Dosage forms
FormRouteStrength
Capsuleoral10 mg/1
Capsuleoral17.5 mg/1
Capsuleoral22.5 mg/1
Capsuleoral25 mg/1
Capsuleoral10 mg
Capsuleoral25 mg
Prices
Unit descriptionCostUnit
Soriatane 17.5 mg capsule30.21USD capsule
Soriatane 22.5 mg capsule30.21USD capsule
Soriatane 25 mg capsule21.71USD capsule
Soriatane 10 mg capsule13.25USD capsule
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 Solubility0.000478 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity104.17 m3·mol-1ChemAxon
Polarizability38.54 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

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

US20040192949
General ReferencesNot Available
External Links
ATC CodesD05BB02
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelDownload (530 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
ChlorotrianiseneThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Acitretin.
DienogestThe therapeutic efficacy of Dienogest can be decreased when used in combination with Acitretin.
EthanolEthanol may increase the activities of Acitretin.
EtonogestrelThe therapeutic efficacy of Etonogestrel can be decreased when used in combination with Acitretin.
LevonorgestrelThe therapeutic efficacy of Levonorgestrel can be decreased when used in combination with Acitretin.
Medroxyprogesterone acetateThe therapeutic efficacy of Medroxyprogesterone Acetate can be decreased when used in combination with Acitretin.
MethotrexateAcitretin may increase the hepatotoxic activities of Methotrexate.
NorethisteroneThe therapeutic efficacy of Norethindrone can be decreased when used in combination with Acitretin.
OxytetracyclineThe risk or severity of adverse effects can be increased when Oxytetracycline is combined with Acitretin.
PorfimerAcitretin may increase the photosensitizing activities of Porfimer.
VerteporfinAcitretin may increase the photosensitizing activities of Verteporfin.
Vitamin AThe risk or severity of adverse effects can be increased when Vitamin A is combined with Acitretin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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 RXR...
Gene Name:
RXRA
Uniprot ID:
P19793
Molecular Weight:
50810.835 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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 RX...
Gene Name:
RARA
Uniprot ID:
P10276
Molecular Weight:
50770.805 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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 ho...
Gene Name:
RARB
Uniprot ID:
P10826
Molecular Weight:
50488.63 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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 m...
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. [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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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 bin...
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. [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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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 RXR...
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. [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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Transporter activity
Specific Function:
Intracellular transport of retinol.
Gene Name:
RBP1
Uniprot ID:
P09455
Molecular Weight:
15850.13 Da
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 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Retinoic acid binding
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:
56198.11 Da
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 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
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:1449542 ]
  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:15902381 ]
  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:2146977 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23