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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
Avage
Tazarotene
Tazaroteno
Tazarotenum
Tazorac
Zorac
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Avagecream1 mg/gcutaneousAllergan, Inc.2003-01-07Not applicableUs
Fabioraerosol, foam1 mg/gtopicalStiefel Laboratories, Inc.2013-09-04Not applicableUs
Tazoracgel1 mg/gcutaneousAllergan, Inc.1997-08-01Not applicableUs
Tazoracgel1 mg/goralPhysicians Total Care, Inc.2010-10-21Not applicableUs
Tazoraccream0.1 %topicalAllergan Inc2001-08-31Not applicableCanada
Tazoraccream1 mg/gcutaneousAllergan, Inc.2000-11-13Not applicableUs
Tazoraccream0.05 %topicalAllergan Inc2001-08-31Not applicableCanada
Tazoraccream.5 mg/gcutaneousAllergan, Inc.2000-11-15Not applicableUs
Tazoracgel0.1 %topicalAllergan Inc1997-04-10Not applicableCanada
Tazoracgel.5 mg/gcutaneousAllergan, Inc.1997-08-01Not applicableUs
Tazoracgel0.05 %topicalAllergan Inc1997-04-10Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ZoracNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII81BDR9Y8PS
CAS number118292-40-3
WeightAverage: 351.462
Monoisotopic: 351.129299611
Chemical FormulaC21H21NO2S
InChI KeyInChIKey=OGQICQVSFDPSEI-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
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
  • Tazarotene
  • Thiochromane
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Alkylarylthioether
  • Benzenoid
  • Thiopyran
  • Pyridine
  • Heteroaromatic compound
  • Carboxylic acid ester
  • Azacycle
  • Organoheterocyclic compound
  • Thioether
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.9936
Blood Brain Barrier+0.9675
Caco-2 permeable+0.5233
P-glycoprotein substrateSubstrate0.5758
P-glycoprotein inhibitor IInhibitor0.5422
P-glycoprotein inhibitor IINon-inhibitor0.5926
Renal organic cation transporterNon-inhibitor0.8219
CYP450 2C9 substrateNon-substrate0.7308
CYP450 2D6 substrateNon-substrate0.7687
CYP450 3A4 substrateSubstrate0.5187
CYP450 1A2 substrateInhibitor0.6172
CYP450 2C9 inhibitorInhibitor0.6385
CYP450 2D6 inhibitorNon-inhibitor0.8531
CYP450 2C19 inhibitorInhibitor0.6586
CYP450 3A4 inhibitorNon-inhibitor0.6387
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6124
Ames testNon AMES toxic0.8154
CarcinogenicityNon-carcinogens0.8925
BiodegradationNot ready biodegradable0.9946
Rat acute toxicity2.5435 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9968
hERG inhibition (predictor II)Non-inhibitor0.7757
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Allergan inc
Packagers
Dosage forms
FormRouteStrength
Aerosol, foamtopical1 mg/g
Creamcutaneous.5 mg/g
Creamcutaneous1 mg/g
Creamtopical0.05 %
Creamtopical0.1 %
Gelcutaneous.5 mg/g
Gelcutaneous1 mg/g
Geloral1 mg/g
Geltopical0.05 %
Geltopical0.1 %
Prices
Unit descriptionCostUnit
Tazorac 0.1% Gel 100 gm Tube638.75USD tube
Tazorac 0.05% Gel 100 gm Tube601.14USD tube
Tazorac 60 gm Tube .1% 60 gm Tube383.22USD tube
Tazorac 60 gm Tube .05% 60 gm Tube360.72USD tube
Tazorac 0.1% Gel 30 gm Tube191.64USD tube
Tazorac 30 gm Tube .1% 30 gm Tube191.64USD tube
Tazorac 0.05% Cream 30 gm Tube180.39USD tube
Tazorac 0.05% Gel 30 gm Tube180.39USD tube
Tazorac 0.1% cream5.59USD g
Tazorac 0.05% cream5.26USD g
Tazorac 0.05 % Gel1.49USD g
Tazorac 0.1 % Gel1.49USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2191773 No2004-08-102015-08-10Canada
US5089509 No1994-06-132011-06-13Us
US5914334 No1994-06-072014-06-07Us
US8808716 No2010-02-242030-02-24Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilitySolubleNot Available
logP5.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00075 mg/mLALOGPS
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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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 ReferencesNot Available
External Links
ATC CodesD05AX05
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelDownload (90.3 KB)
MSDSDownload (25.7 KB)
Interactions
Drug InteractionsNo interactions found.
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 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. 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:16144296 ]
  2. Chandraratna RA: Tazarotene--first of a new generation of receptor-selective retinoids. Br J Dermatol. 1996 Oct;135 Suppl 49:18-25. [PubMed:9035701 ]
  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:15383624 ]
  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:14675762 ]
  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:11519864 ]
  6. Nagpal S, Chandraratna RA: Recent developments in receptor-selective retinoids. Curr Pharm Des. 2000 Jun;6(9):919-31. [PubMed:10828316 ]
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 ]
  3. Nagpal S, Chandraratna RA: Recent developments in receptor-selective retinoids. Curr Pharm Des. 2000 Jun;6(9):919-31. [PubMed:10828316 ]
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 ]
  4. Arechalde A, Saurat JH: Management of psoriasis: the position of retinoid drugs. BioDrugs. 2000 May;13(5):327-33. [PubMed:18034539 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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. 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:12942109 ]
  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:15102095 ]
  3. Chandraratna RA: Tazarotene--first of a new generation of receptor-selective retinoids. Br J Dermatol. 1996 Oct;135 Suppl 49:18-25. [PubMed:9035701 ]
  4. Arechalde A, Saurat JH: Management of psoriasis: the position of retinoid drugs. BioDrugs. 2000 May;13(5):327-33. [PubMed:18034539 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 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 ]
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Drug created on June 13, 2005 07:24 / Updated on July 30, 2016 01:53