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Identification
NameTazarotene
Accession NumberDB00799  (APRD01246)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Tazarotene (marketed as Tazorac®, Avage® and Zorac®) is a prescription topical retinoid sold as a cream or gel. This medication is approved for treatment of psoriasis, acne, and sun damaged skin (photodamage). [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
AvageNot AvailableNot Available
TazaroteneNot AvailableINN, USAN
TazarotenoNot AvailableNot Available
TazarotenumNot AvailableNot Available
TazoracNot AvailableNot Available
ZoracNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
FabiorNot Available
TazoracNot Available
ZoracNot Available
Brand mixturesNot Available
Categories
CAS number118292-40-3
WeightAverage: 351.462
Monoisotopic: 351.129299611
Chemical FormulaC21H21NO2S
InChI KeyOGQICQVSFDPSEI-UHFFFAOYSA-N
InChI
InChI=1S/C21H21NO2S/c1-4-24-20(23)16-7-9-17(22-14-16)8-5-15-6-10-19-18(13-15)21(2,3)11-12-25-19/h6-7,9-10,13-14H,4,11-12H2,1-3H3
IUPAC Name
ethyl 6-[2-(4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran-6-yl)ethynyl]pyridine-3-carboxylate
SMILES
CCOC(=O)C1=CN=C(C=C1)C#CC1=CC2=C(SCCC2(C)C)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassPrenol Lipids
SubclassRetinoids
Direct parentRetinoids
Alternative parentsThiochromanes; Pyridinecarboxylic Acids; Thiopyrans; Benzene and Substituted Derivatives; Carboxylic Acid Esters; Dialkyl Ethers; Enolates; Thioethers; Polyamines
Substituentsthiochromane; pyridine carboxylic acid; pyridine carboxylic acid or derivative; pyridine; thiopyran; benzene; carboxylic acid ester; enolate; thioether; polyamine; ether; dialkyl ether; carboxylic acid derivative; organonitrogen compound
Classification descriptionThis compound belongs to the retinoids. These are compounds that are related to vitamin A, especially retinol.
Pharmacology
IndicationUsed to treat psoriasis, acne and sun damaged skin (photodamage).
PharmacodynamicsTazarotene is a prodrug and a member of the acetylenic class of retinoids. Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. When treating acne tazarotene may be taken in conjunction with an oral antibiotic. Tazarotene has been shown in peer-reviewed double blinded studies to reduce: mottling and hyperpigmentation, sallowness, fine wrinkling and coarse wrinkling in sun damaged skin. Histological studies have shown that long term (greater than 1 year) use of Tazarotene is associated with a significant reduction in atypical melanocytes and keratocytes - cells considered to be precursors of skin cancer. Some studies have shown long term use of Tazarotene to be associated with increased collagen production and better organization of skin collagen bundles.
Mechanism of actionAlthough the exact mechanism of tazarotene action is not known, studies have shown that the active form of the drug (tazarotenic acid) binds to all three members of the retinoic acid receptor (RAR) family: RARa, RARb, and RARg, but shows relative selectivity for RARb, and RARg and may modify gene expression. It also has affinity for RXR receptors.
AbsorptionMinimal systemic absorption of tazarotene occurs due to its rapid metabolism in the skin to the active metabolite, tazarotenic acid, which can be systemically absorbed and further metabolized. Gender had no influence on the systemic bioavailability of tazarotenic acid.
Volume of distributionNot Available
Protein bindingThe active form of the drug, tazarotenic acid, is highly bound to plasma proteins (>99%).
Metabolism

Undergoes esterase hydrolysis in skin to form its active metabolite, tazarotenic acid. Tazarotenic acid is further metabolized in skin and, after systemic absorption, hepatically metabolized to sulfoxides, sulfones, and other polar products for elimination.

SubstrateEnzymesProduct
Tazarotene
Not Available
Tazarotenic acidDetails
Route of eliminationTazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways.
Half lifeThe half-life of the active form of the drug, tazarotenic acid, is approximately 18 hours in normal and psoriatic patients.
ClearanceNot Available
ToxicityExcessive topical use may lead to marked redness, peeling, or discomfort. Oral ingestion of the drug may affect liver function causing hypertriglyceridemia. Other symptoms may include conjunctival irritation, hair loss, headache, edema, fatigue, dermatitis, nausea, and visual disturbances. Oral administration of this material to rats and rabbits at doses of 0.20 mg/kg/day (rabbits) and 0.25 mg/kg/day (rats) resulted in developmental toxicity. A no effect level of 0.05 mg/kg/day was established. Similar teratogenic effects have been reported for other retinoid compounds.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9936
Blood Brain Barrier + 0.9675
Caco-2 permeable + 0.5233
P-glycoprotein substrate Substrate 0.5758
P-glycoprotein inhibitor I Inhibitor 0.5422
P-glycoprotein inhibitor II Non-inhibitor 0.5926
Renal organic cation transporter Non-inhibitor 0.8219
CYP450 2C9 substrate Non-substrate 0.7308
CYP450 2D6 substrate Non-substrate 0.7687
CYP450 3A4 substrate Substrate 0.5187
CYP450 1A2 substrate Inhibitor 0.6172
CYP450 2C9 substrate Inhibitor 0.6385
CYP450 2D6 substrate Non-inhibitor 0.8531
CYP450 2C19 substrate Inhibitor 0.6586
CYP450 3A4 substrate Non-inhibitor 0.6387
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6124
Ames test Non AMES toxic 0.8154
Carcinogenicity Non-carcinogens 0.8925
Biodegradation Not ready biodegradable 0.9946
Rat acute toxicity 2.5435 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9968
hERG inhibition (predictor II) Non-inhibitor 0.7757
Pharmacoeconomics
Manufacturers
  • Allergan inc
Packagers
Dosage forms
FormRouteStrength
CreamTopical
GelTopical
Prices
Unit descriptionCostUnit
Tazorac 0.1% Gel 100 gm Tube638.75USDtube
Tazorac 0.05% Gel 100 gm Tube601.14USDtube
Tazorac 60 gm Tube .1% 60 gm Tube383.22USDtube
Tazorac 60 gm Tube .05% 60 gm Tube360.72USDtube
Tazorac 0.1% Gel 30 gm Tube191.64USDtube
Tazorac 30 gm Tube .1% 30 gm Tube191.64USDtube
Tazorac 0.05% Cream 30 gm Tube180.39USDtube
Tazorac 0.05% Gel 30 gm Tube180.39USDtube
Tazorac 0.1% cream5.59USDg
Tazorac 0.05% cream5.26USDg
Tazorac 0.05 % Gel1.49USDg
Tazorac 0.1 % Gel1.49USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States59143341994-06-072014-06-07
United States50895091994-06-132011-06-13
Canada21917732004-08-102015-08-10
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilitySolubleNot Available
logP5.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00075ALOGPS
logP5.15ALOGPS
logP5.22ChemAxon
logS-5.7ALOGPS
pKa (Strongest Basic)1.23ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area39.19 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity97.88 m3·mol-1ChemAxon
Polarizability40.31 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Samuele Frigoli, Claudio Fuganti, Stefano Serra, Francesco Pizzocaro, Angelo Bedeschi, Paolo Tubertini, “Process for the preparation of Tazarotene.” U.S. Patent US20060205950, issued September 14, 2006.

US20060205950
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD01132
KEGG CompoundC12531
PubChem Compound5381
PubChem Substance46508992
ChemSpider5188
ChEBI32184
ChEMBLCHEMBL1657
Therapeutic Targets DatabaseDAP000462
PharmGKBPA164746821
Drug Product Database2243894
RxListhttp://www.rxlist.com/cgi/generic3/avage.htm
Drugs.comhttp://www.drugs.com/cdi/tazarotene-cream.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/taz1429.shtml
WikipediaTazarotene
ATC CodesD05AX05
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelshow(90.3 KB)
MSDSshow(25.7 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. 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. Baumann L, Vujevich J, Halem M, Martin LK, Kerdel F, Lazarus M, Pacheco H, Black L, Bryde J: Open-label pilot study of alitretinoin gel 0.1% in the treatment of photoaging. Cutis. 2005 Jul;76(1):69-73. Pubmed
  2. Chandraratna RA: Tazarotene—first of a new generation of receptor-selective retinoids. Br J Dermatol. 1996 Oct;135 Suppl 49:18-25. Pubmed
  3. Yen A, Fenning R, Chandraratna R, Walker P, Varvayanis S: A retinoic acid receptor beta/gamma-selective prodrug (tazarotene) plus a retinoid X receptor ligand induces extracellular signal-regulated kinase activation, retinoblastoma hypophosphorylation, G0 arrest, and cell differentiation. Mol Pharmacol. 2004 Dec;66(6):1727-37. Epub 2004 Sep 21. Pubmed
  4. Meder W, Wendland M, Busmann A, Kutzleb C, Spodsberg N, John H, Richter R, Schleuder D, Meyer M, Forssmann WG: Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23. FEBS Lett. 2003 Dec 18;555(3):495-9. Pubmed
  5. Wang Q, Lee D, Sysounthone V, Chandraratna RAS, Christakos S, Korah R, Wieder R: 1,25-dihydroxyvitamin D3 and retonic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects. Breast Cancer Res Treat. 2001 May;67(2):157-68. Pubmed
  6. Nagpal S, Chandraratna RA: Recent developments in receptor-selective retinoids. Curr Pharm Des. 2000 Jun;6(9):919-31. Pubmed

2. 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
  3. Nagpal S, Chandraratna RA: Recent developments in receptor-selective retinoids. Curr Pharm Des. 2000 Jun;6(9):919-31. Pubmed

3. 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
  4. Arechalde A, Saurat JH: Management of psoriasis: the position of retinoid drugs. BioDrugs. 2000 May;13(5):327-33. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. 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. Jones PH, Burnett RD, Fainaru I, Nadolny P, Walker P, Yu Z, Tang-Liu D, Ganesan TS, Talbot DC, Harris AL, Rustin GJ: A phase 1 study of tazarotene in adults with advanced cancer. Br J Cancer. 2003 Sep 1;89(5):808-15. Pubmed
  2. Orlandi A, Bianchi L, Costanzo A, Campione E, Giusto Spagnoli L, Chimenti S: Evidence of increased apoptosis and reduced proliferation in basal cell carcinomas treated with tazarotene. J Invest Dermatol. 2004 Apr;122(4):1037-41. Pubmed
  3. Chandraratna RA: Tazarotene—first of a new generation of receptor-selective retinoids. Br J Dermatol. 1996 Oct;135 Suppl 49:18-25. Pubmed
  4. Arechalde A, Saurat JH: Management of psoriasis: the position of retinoid drugs. BioDrugs. 2000 May;13(5):327-33. Pubmed

Enzymes

1. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12