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Identification
Name Tazarotene
Accession Number DB00799 (APRD01246)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Tazarotene [USAN:INN]
Tazorac
Zorac
Brand mixtures Not Available
Categories
  • Keratolytic Agents
  • Dermatologic Agents
  • Prodrugs
  • Teratogens
CAS number 118292-40-3
Weight Average: 351.462
Monoisotopic: 351.129299611
Chemical Formula C21H21NO2S
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Retinoids
Substructures
  • Carboxylic Acids and Derivatives
  • Ethers
  • Acetates
  • Alkynes
  • Pyridines and Derivatives
  • Benzene and Derivatives
  • Retinoids
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
Pharmacology
Indication Used to treat psoriasis, acne and sun damaged skin (photodamage).
Pharmacodynamics Tazarotene 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 action Although 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.
Absorption Minimal 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 distribution Not Available
Protein binding The 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.
Route of elimination Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways.
Half life The half-life of the active form of the drug, tazarotenic acid, is approximately 18 hours in normal and psoriatic patients.
Clearance Not Available
Toxicity Excessive 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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Allergan inc
Packagers
Dosage forms
Form Route Strength
Cream Topical
Gel Topical
Prices
Unit description Cost Unit
Tazorac 0.1% Gel 100 gm Tube 638.75 USD tube
Tazorac 0.05% Gel 100 gm Tube 601.14 USD tube
Tazorac 60 gm Tube .1% 60 gm Tube 383.22 USD tube
Tazorac 60 gm Tube .05% 60 gm Tube 360.72 USD tube
Tazorac 0.1% Gel 30 gm Tube 191.64 USD tube
Tazorac 30 gm Tube .1% 30 gm Tube 191.64 USD tube
Tazorac 0.05% Cream 30 gm Tube 180.39 USD tube
Tazorac 0.05% Gel 30 gm Tube 180.39 USD tube
Tazorac 0.1% cream 5.59 USD g
Tazorac 0.05% cream 5.26 USD g
Tazorac 0.05 % Gel 1.49 USD g
Tazorac 0.1 % Gel 1.49 USD g
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Patents
Country Patent Number Approved Expires (estimated)
United States 5914334 1994-06-07 2014-06-07
United States 5089509 1994-06-13 2011-06-13
Canada 2191773 2004-08-10 2015-08-10
Properties
State solid
Experimental Properties
Property Value Source
water solubility Soluble Not Available
logP 5.6 Not Available
Predicted Properties
Property Value Source
water solubility 7.50e-04 g/l ALOGPS
logP 5.15 ALOGPS
logP 5.22 ChemAxon
logS -5.7 ALOGPS
pKa (strongest basic) 1.23 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 39.19 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 97.88 ChemAxon
polarizability 40.31 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D01132 Link_out
KEGG Compound C12531 Link_out
PubChem Compound 5381 Link_out
PubChem Substance 46508992 Link_out
ChemSpider 5188 Link_out
ChEBI 32184 Link_out
ChEMBL 32184 Link_out
Therapeutic Targets Database DAP000462 Link_out
PharmGKB PA164746821 Link_out
Drug Product Database 2243894 Link_out
RxList http://www.rxlist.com/cgi/generic3/avage.htm Link_out
Drugs.com http://www.drugs.com/cdi/tazarotene-cream.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/taz1429.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Tazarotene Link_out
ATC Codes
  • D05AX05
AHFS Codes
  • 84:92.00
PDB Entries Not Available
FDA label show (90.3 KB)
MSDS show (25.7 KB)
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. Retinoic acid receptor alpha

Pharmacological action: yes
Actions: agonist

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

Organism class: human
UniProt ID: P10276 Link_out
Gene: RARA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA)

Organism class: human
UniProt ID: P28702 Link_out
Gene: RXRB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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-1

Pharmacological action: yes
Actions: agonist

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

Organism class: human
UniProt ID: P13631 Link_out
Gene: RARG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

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

Organism class: human
UniProt ID: P10826 Link_out
Gene: RARB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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 responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19