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Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:51
Primary Accession Number DB00549
Secondary Accession Number
  • APRD00377
Name Zafirlukast
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Zafirlukast is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Another leukotriene receptor antagonist is montelukast (Singulair), which is usually taken just once daily. Zafirlukast blocks the action of the cysteinyl leukotrienes on the CysLT1 receptors, thus reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages.
Synonyms
  1. zafirlukast
Brand Names
  1. Accolate
Brand Mixtures Not Available
Chemical IUPAC Name cyclopentyl N-[3-[[2-methoxy-4-[(2-methylphenyl)sulfonylcarbamoyl]phenyl]methyl]-1-methylindol-5-yl]carbamate
Chemical Formula C31H33N3O6S
Chemical Structure Structure
CAS Registry Number 107753-78-6
InChI Identifier InChI=1/C31H33N3O6S/c1-20-8-4-7-11-29(20)41(37,38)33-30(35)22-13-12-21(28(17-22)39-3)16-23-19-34(2)27-15-14-24(18-26(23)27)32-31(36)40-25-9-5-6-10-25/h4,7-8,11-15,17-19,25H,5-6,9-10,16H2,1-3H3,(H,32,36)(H,33,35)/f/h32-33H
InChI Key YEEZWCHGZNKEEK-MJHPXVFFCO
KEGG Drug D00411 Link Image
KEGG Compound C07206 Link Image
PubChem Compound 5717 Link Image
PubChem Substance 196556 Link Image
ChEBI ID 10100 Link Image
PharmGKB ID PA451949 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02236606 Link Image
RxList Link http://www.rxlist.com/cgi/generic/zafirlukast.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Zafirlukast Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference F. J. Brown et al., Eur. pat. Appl. 199,543; P. R. Bernstein et al., U.S. pat. 4,859,692 (1986, 1989 both to ICI)
Average Molecular Weight 575.6750
Monoisotopic Molecular Weight 575.2090
State Solid
Melting Point 139 oC
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 9.62e-04 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 5.4 Source: PhysProp
Predicted LogP 4.84 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -5.78 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES COC1=C(CC2=CN(C)C3=C2C=C(NC(=O)OC2CCCC2)C=C3)C=CC(=C1)C(=O)NS(=O)(=O)C1=CC=CC=C1C
Canonical SMILES COC1=C(CC2=CN(C)C3=C2C=C(NC(=O)OC2CCCC2)C=C3)C=CC(=C1)C(=O)NS(=O)(=O)C1=CC=CC=C1C
Drug Category
  • Anti-Asthmatic Agents
  • Leukotriene Antagonists
ATC Codes
AHFS Codes
  • 48:10.24
Indication For the prophylaxis and chronic treatment of asthma.
Pharmacology Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA) indicated for the prophylaxis and chronic treatment of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD4 than nonasthmatic subjects. In vitro studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4 and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited inhaled LTD4-induced influx of eosinophils into animal lungs.
Mechanism of Action Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.
Absorption Rapidly absorbed following oral administration, reduced following a high-fat or high-protein meal.
Toxicity Side effects include rash and upset stomach.
Protein Binding 99%
Biotransformation Hepatic
Half Life 10 hours
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol Zafirlukast may inhibit the metabolism of the vitamin K antagonist Acenocoumarol and increase INR and risk of bleeding.
Aminophylline Zafirlukast serum concentrations may be decreased by the theophylline derivative Aminophylline.
Aminosalicylic Acid Zafirlukast serum concentrations may be increased by the salicylate Aminosalicylic Acid.
Aspirin Zafirlukast serum concentrations may be increased by the salicylate Aspirin.
Erythromycin Zafirlukast serum concentrations may be decreased by Erythromycin.
Salicyclic acid Zafirlukast serum concentrations may be increased by the salicylate Salicyclic Acid.
Salicylate-magnesium Zafirlukast serum concentrations may be increased by the salicylate Magnesium Salicylate.
Salicylate-sodium Zafirlukast serum concentrations may be increased by the salicylate Sodium Salicylate.
Salsalate Zafirlukast serum concentrations may be increased by the salicylate Salsalate.
Theophylline Zafirlukast serum concentrations may be decreased by the theophylline derivative Theophylline.
Food Interactions
  • Take on empty stomach: 1 hour before or 2 hours after meals.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C8 (CYP2C8)
  2. Cytochrome P450 2C9 (CYP2C9)
Targets
  1. Cysteinyl leukotriene receptor 1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C8 (CYP2C8)
Enzyme 1 Gene Name CYP2C8
Enzyme 1 SwissProt ID P10632 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P10632|CP2C8_HUMAN Cytochrome P450 2C8 (EC 1.14.14.1) 
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKV
YGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRW
KEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICS
VVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALT
RSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTE
TTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSD
LVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFK
KSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLP
PSYQICFIPV
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 2C9 (CYP2C9)
Enzyme 2 Gene Name CYP2C9
Enzyme 2 SwissProt ID P11712 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P11712|CP2C9_HUMAN Cytochrome P450 2C9 (EC 1.14.13.80) 
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV
Drug Target 1 [top]
Target 1 ID 778
Target 1 Name Cysteinyl leukotriene receptor 1
Target 1 Synonyms
  1. CysLTR1
  2. Cysteinyl leukotriene D4 receptor
  3. HG55
  4. HMTMF81
  5. LTD4 receptor
Target 1 Gene Name CYSLTR1
Target 1 Protein Sequence >Cysteinyl leukotriene receptor 1 
MDETGNLTVSSATCHDTIDDFRNQVYSTLYSMISVVGFFGNGFVLYVLIKTYHKKSAFQV
YMINLAVADLLCVCTLPLRVVYYVHKGIWLFGDFLCRLSTYALYVNLYCSIFFMTAMSFF
RCIAIVFPVQNINLVTQKKARFVCVGIWIFVILTSSPFLMAKPQKDEKNNTKCFEPPQDN
QTKNHVLVLHYVSLFVGFIIPFVIIIVCYTMIILTLLKKSMKKNLSSHKKAIGMIMVVTA
AFLVSFMPYHIQRTIHLHFLHNETKPCDSVLRMQKSVVITLSLAASNCCFDPLLYFFSGG
NFRKRLSTFRKHSLSSVTYVPRKKASLPEKGEEICKV
Target 1 Number of Residues 342
Target 1 Molecular Weight 38541
Target 1 Theoretical pI 9.68
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
leukotriene receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in leukotriene receptor activity
Target 1 Specific Function Receptor for cysteinyl leukotrienes mediating bronchoconstriction of individuals with and without asthma. Stimulation by LTD4 results in the contraction and proliferation of smooth muscle, edema, eosinophil migration and damage to the mucus layer in the lung. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTD4 >> LTE4 = LTC4 >> LTB4
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 29-49
  • 58-78
  • 107-127
  • 142-162
  • 194-214
  • 231-251
  • 277-297
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 5353887 Link Image
Target 1 UniProtKB/Swiss-Prot ID Q9Y271 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name CLTR1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1014 bp 
ATGGATGAAACAGGAAATCTGACAGTATCTTCTGCCACATGCCATGACACTATTGATGAC
TTCCGCAATCAAGTGTATTCCACCTTGTACTCTATGATCTCTGTTGTAGGCTTCTTTGGC
AATGGCTTTGTGCTCTATGTCCTCATAAAAACCTATCACAAGAAGTCAGCCTTCCAAGTA
TACATGATTAATTTAGCAGTAGCAGATCTACTTTGTGTGTGCACACTGCCTCTCCGTGTG
GTCTATTATGTTCACAAAGGCATTTGGCTCTTTGGTGACTTCTTGTGCCGCCTCAGCACC
TATGCTTTGTATGTCAACCTCTATTGTAGCATCTTCTTTATGACAGCCATGAGCTTTTTC
CGGTGCATTGCAATTGTTTTTCCAGTCCAGAACATTAATTTGGTTACACAGAAAAAAGCC
AGGTTTGTGTGTGTAGGTATTTGGATTTTTGTGATTTTGACCAGTTCTCCATTTCTAATG
GCCAAACCACAAAAAGATGAGAAAAATAATACCAAGTGCTTTGAGCCCCCACAAGACAAT
CAAACTAAAAATCATGTTTTGGTCTTGCATTATGTGTCATTGTTTGTTGGCTTTATCATC
CCTTTTGTTATTATAATTGTCTGTTACACAATGATCATTTTGACCTTACTAAAAAAATCA
ATGAAAAAAAATCTGTCAAGTCATAAAAAGGCTATAGGAATGATCATGGTCGTGACCGCT
GCCTTTTTAGTCAGTTTCATGCCATATCATATTCAACGTACCATTCACCTTCATTTTTTA
CACAATGAAACTAAACCCTGTGATTCTGTCCTTAGAATGCAGAAGTCCGTGGTCATAACC
TTGTCTCTGGCTGCATCCAATTGTTGCTTTGACCCTCTCCTATATTTCTTTTCTGGGGGT
AACTTTAGGAAAAGGCTGTCTACATTTAGAAAGCATTCTTTGTCCAGCGTGACTTATGTA
CCCAGAAAGAAGGCCTCTTTGCCAGAAAAAGGAGAAGAAATATGTAAAGTATAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID CYSLTR1 Link Image
Target 1 GenAtlas ID CYSLTR1 Link Image
Target 1 HGNC ID HGNC:17451 Link Image
Target 1 Chromosome Location X
Target 1 Locus Xq13.2-21.1
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Lynch KR, O'Neill GP, Liu Q, Im DS, Sawyer N, Metters KM, Coulombe N, Abramovitz M, Figueroa DJ, Zeng Z, Connolly BM, Bai C, Austin CP, Chateauneuf A, Stocco R, Greig GM, Kargman S, Hooks SB, Hosfield E, Williams DL Jr, Ford-Hutchinson AW, Caskey CT, Evans JF: Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature. 1999 Jun 24;399(6738):789-93. [PubMed Link Image]
  2. Sarau HM, Ames RS, Chambers J, Ellis C, Elshourbagy N, Foley JJ, Schmidt DB, Muccitelli RM, Jenkins O, Murdock PR, Herrity NC, Halsey W, Sathe G, Muir AI, Nuthulaganti P, Dytko GM, Buckley PT, Wilson S, Bergsma DJ, Hay DW: Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor. Mol Pharmacol. 1999 Sep;56(3):657-63. [PubMed Link Image]
Target 1 Drug References
  1. Heise CE, O'Dowd BF, Figueroa DJ, Sawyer N, Nguyen T, Im DS, Stocco R, Bellefeuille JN, Abramovitz M, Cheng R, Williams DL Jr, Zeng Z, Liu Q, Ma L, Clements MK, Coulombe N, Liu Y, Austin CP, George SR, O'Neill GP, Metters KM, Lynch KR, Evans JF: Characterization of the human cysteinyl leukotriene 2 receptor. J Biol Chem. 2000 Sep 29;275(39):30531-6. [PubMed Link Image]
  2. Wang S, Gustafson E, Pang L, Qiao X, Behan J, Maguire M, Bayne M, Laz T: A novel hepatointestinal leukotriene B4 receptor. Cloning and functional characterization. J Biol Chem. 2000 Dec 29;275(52):40686-94. [PubMed Link Image]
  3. Cazzola M, Boveri B, Carlucci P, Santus P, DiMarco F, Centanni S, Allegra L: Lung function improvement in smokers suffering from COPD with zafirlukast, a CysLT(1)-receptor antagonist. Pulm Pharmacol Ther. 2000;13(6):301-5. [PubMed Link Image]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  5. Murata Y, Sugimoto O: [Zafirlukast (Accolate): a review of its pharmacological and clinical profile] Nippon Yakurigaku Zasshi. 2002 Apr;119(4):247-58. [PubMed Link Image]
  6. O'Byrne PM: Leukotrienes in the pathogenesis of asthma. Chest. 1997 Feb;111(2 Suppl):27S-34S. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.