Zafirlukast

Identification

Summary

Zafirlukast is a leukotriene receptor antagonist used for prophylaxis and chronic treatment of asthma.

Brand Names
Accolate
Generic Name
Zafirlukast
DrugBank Accession Number
DB00549
Background

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 575.675
Monoisotopic: 575.209006493
Chemical Formula
C31H33N3O6S
Synonyms
  • 4-(5-cyclopentyloxycarbonylamino-1-methyl-1H-indol-3-ylmethyl)-3-methoxy-N-o-tolylsulfonylbenzamide
  • cyclopentyl 3-(2-methoxy-4-((o-tolylsulfonyl)carbamoyl)benzyl)-1-methylindole-5-carbamate
  • Zafirlukast
External IDs
  • ICI 204,219
  • ICI-204,219
  • ICI-204219

Pharmacology

Indication

For the prophylaxis and chronic treatment of asthma.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAsthma••••••••••••
Treatment ofChronic urticaria••• •••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

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.

TargetActionsOrganism
ACysteinyl leukotriene receptor 1
antagonist
Humans
Absorption

Rapidly absorbed following oral administration, reduced following a high-fat or high-protein meal.

Volume of distribution
  • 70 L
Protein binding

99%

Metabolism

Hepatic

Hover over products below to view reaction partners

Route of elimination

The most common metabolic products are hydroxylated metabolites which are excreted in the feces.

Half-life

10 hours

Clearance
  • apparent oral CL=20 L/h
  • 11.4 L/h [7-11 yrs]
  • 9.2 L/h [5-6 yrs]
Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Side effects include rash and upset stomach.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe metabolism of Zafirlukast can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Zafirlukast.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Zafirlukast.
AcalabrutinibThe serum concentration of Acalabrutinib can be increased when it is combined with Zafirlukast.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Zafirlukast.
Food Interactions
  • Take on an empty stomach. Take at least 1 hour before or 2 hours after meals.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AccolateTablet, film coated20 mg/1OralAstra Zeneca Lp1996-10-012017-09-29US flag
AccolateTablet, film coated20 mg/1OralStrides Pharma Science Limited2023-01-02Not applicableUS flag
AccolateTablet, film coated20 mg/1OralPhysicians Total Care, Inc.1996-09-262011-09-30US flag
AccolateTablet, film coated20 mg/1OralPar Pharmaceutical Inc.2015-01-092017-09-30US flag
AccolateTablet, film coated10 mg/1OralStrides Pharma Science Limited2023-01-02Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ZafirlukastTablet10 mg/1OralRising Pharmaceuticals, Inc.2022-08-25Not applicableUS flag
ZafirlukastTablet, film coated20 mg/1OralAvPAK2017-09-15Not applicableUS flag
ZafirlukastTablet, film coated10 mg/1OralDr. Reddys Laboratories Limited2010-11-18Not applicableUS flag
ZafirlukastTablet, film coated10 mg/1OralAurobindo Pharma Limited2023-11-27Not applicableUS flag
ZafirlukastTablet, film coated20 mg/1OralCamber Pharmaceuticals, Inc.2020-09-10Not applicableUS flag

Categories

ATC Codes
R03DC01 — Zafirlukast
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
3-alkylindoles / N-alkylindoles / Benzenesulfonyl compounds / Benzoic acids and derivatives / Phenoxy compounds / Benzoyl derivatives / Anisoles / Methoxybenzenes / Toluenes / Alkyl aryl ethers
show 12 more
Substituents
3-alkylindole / Alkyl aryl ether / Aminosulfonyl compound / Anisole / Aromatic heteropolycyclic compound / Azacycle / Benzenesulfonamide / Benzenesulfonyl group / Benzoic acid or derivatives / Benzoyl
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
carbamate ester, sulfonamide, indoles (CHEBI:10100)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
XZ629S5L50
CAS number
107753-78-6
InChI Key
YEEZWCHGZNKEEK-UHFFFAOYSA-N
InChI
InChI=1S/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)
IUPAC Name
cyclopentyl N-[3-({2-methoxy-4-[(2-methylbenzenesulfonyl)carbamoyl]phenyl}methyl)-1-methyl-1H-indol-5-yl]carbamate
SMILES
COC1=CC(=CC=C1CC1=CN(C)C2=C1C=C(NC(=O)OC1CCCC1)C=C2)C(=O)NS(=O)(=O)C1=CC=CC=C1C

References

Synthesis Reference

Arie Gutman, "Process for the preparation of zafirlukast." U.S. Patent US20040186300, issued September 23, 2004.

US20040186300
General References
Not Available
Human Metabolome Database
HMDB0014689
KEGG Drug
D00411
KEGG Compound
C07206
PubChem Compound
5717
PubChem Substance
46506874
ChemSpider
5515
BindingDB
50009073
RxNav
114970
ChEBI
10100
ChEMBL
CHEMBL603
ZINC
ZINC000000896717
Therapeutic Targets Database
DAP000091
PharmGKB
PA451949
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
ZLK
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Zafirlukast
PDB Entries
6rz5 / 7ypz
FDA label
Download (233 KB)
MSDS
Download (57.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Not Yet RecruitingTreatmentAllergy to Cats1
2RecruitingTreatmentOvarian Cancer1
2TerminatedTreatmentBreast Cancer1
1CompletedTreatmentHealthy Volunteers (HV)1

Pharmacoeconomics

Manufacturers
  • Astrazeneca uk ltd
Packagers
  • AstraZeneca Inc.
  • Cardinal Health
  • IPR Pharmaceuticals Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
  • Zeneca Pharma Inc.
Dosage Forms
FormRouteStrength
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral20 mg
TabletOral20 mg
Tablet, film coatedOral
Tablet, film coatedOral10 mg
Tablet, coatedOral250 mg
TabletOral20.00 mg
TabletOral10 mg/1
TabletOral20 mg/1
Tablet, coatedOral10 mg/1
Tablet, coatedOral20 mg/1
Tablet, film coatedOral10 mg/1
Prices
Unit descriptionCostUnit
Accolate 10 mg tablet1.92USD tablet
Accolate 20 mg tablet1.86USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5612367No1997-03-182014-03-18US flag
US4859692No1989-08-222010-09-26US flag
CA2056066No2002-04-022011-11-22Canada flag
CA1340567No1999-06-012016-06-01Canada flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)139 °CNot Available
logP5.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000962 mg/mLALOGPS
logP4.84ALOGPS
logP6.4Chemaxon
logS-5.8ALOGPS
pKa (Strongest Acidic)4.29Chemaxon
pKa (Strongest Basic)-1.1Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area115.73 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity158.58 m3·mol-1Chemaxon
Polarizability62 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.8849
Blood Brain Barrier+0.9153
Caco-2 permeable-0.6613
P-glycoprotein substrateNon-substrate0.7027
P-glycoprotein inhibitor INon-inhibitor0.6249
P-glycoprotein inhibitor IIInhibitor0.8915
Renal organic cation transporterNon-inhibitor0.8475
CYP450 2C9 substrateNon-substrate0.5189
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5322
CYP450 1A2 substrateNon-inhibitor0.5261
CYP450 2C9 inhibitorInhibitor0.646
CYP450 2D6 inhibitorNon-inhibitor0.8263
CYP450 2C19 inhibitorInhibitor0.5826
CYP450 3A4 inhibitorInhibitor0.7904
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9189
Ames testNon AMES toxic0.6072
CarcinogenicityNon-carcinogens0.7292
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.5723 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9216
hERG inhibition (predictor II)Inhibitor0.7693
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-052f-9330620000-fc40738dd1a7e2c81dc5
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-00di-0001190000-27c5d161a5754e1434f4
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-00di-0001190000-27c5d161a5754e1434f4
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0292-0940000000-f369442eba5344b3ecb4
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0292-0940000000-f369442eba5344b3ecb4
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0003191000-ba3996913abfda3b22c4
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4r-0259300000-1440474b4cb47824c9f2
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0001191000-58bcdb71b459847fc794
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0ap0-0149300000-896e679131032968db95
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-1900270000-06eb659c512cbfd08eed
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-2900020000-2881801382cb9f5d5f9d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-3019330000-2acee3391d6ba1d5b9ef
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-006x-9500340000-478b152044ad573bc250
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00mo-9014130000-40053ee7cf9a32e8de02
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-052o-9300230000-11fa70a9c7e58a3ecb35
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-244.7834039
predicted
DarkChem Lite v0.1.0
[M-H]-263.3453039
predicted
DarkChem Lite v0.1.0
[M-H]-226.52211
predicted
DeepCCS 1.0 (2019)
[M+H]+247.2436039
predicted
DarkChem Lite v0.1.0
[M+H]+264.1508039
predicted
DarkChem Lite v0.1.0
[M+H]+228.70529
predicted
DeepCCS 1.0 (2019)
[M+Na]+247.2219039
predicted
DarkChem Lite v0.1.0
[M+Na]+263.9610039
predicted
DarkChem Lite v0.1.0
[M+Na]+234.6179
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Leukotriene receptor activity
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, e...
Gene Name
CYSLTR1
Uniprot ID
Q9Y271
Uniprot Name
Cysteinyl leukotriene receptor 1
Molecular Weight
38540.55 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. 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. [Article]
  3. Murata Y, Sugimoto O: [Zafirlukast (Accolate): a review of its pharmacological and clinical profile]. Nihon Yakurigaku Zasshi. 2002 Apr;119(4):247-58. [Article]
  4. 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. [Article]
  5. O'Byrne PM: Leukotrienes in the pathogenesis of asthma. Chest. 1997 Feb;111(2 Suppl):27S-34S. [Article]
  6. 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. [Article]
  7. Singh RK, Tandon R, Dastidar SG, Ray A: A review on leukotrienes and their receptors with reference to asthma. J Asthma. 2013 Nov;50(9):922-31. doi: 10.3109/02770903.2013.823447. Epub 2013 Aug 16. [Article]
  8. McMahon B, Mitchell D, Shattock R, Martin F, Brady HR, Godson C: Lipoxin, leukotriene, and PDGF receptors cross-talk to regulate mesangial cell proliferation. FASEB J. 2002 Nov;16(13):1817-9. doi: 10.1096/fj.02-0416fje. Epub 2002 Sep 5. [Article]
  9. Figueroa EE, Kramer M, Strange K, Denton JS: CysLT1 receptor antagonists pranlukast and zafirlukast inhibit LRRC8-mediated volume regulated anion channels independently of the receptor. Am J Physiol Cell Physiol. 2019 Oct 1;317(4):C857-C866. doi: 10.1152/ajpcell.00281.2019. Epub 2019 Aug 7. [Article]
  10. Ruiz I, Nevers Q, Hernandez E, Ahnou N, Brillet R, Softic L, Donati F, Berry F, Hamadat S, Fourati S, Pawlotsky JM, Ahmed-Belkacem A: MK-571, a Cysteinyl Leukotriene Receptor 1 Antagonist, Inhibits Hepatitis C Virus Replication. Antimicrob Agents Chemother. 2020 May 21;64(6). pii: AAC.02078-19. doi: 10.1128/AAC.02078-19. Print 2020 May 21. [Article]
  11. Reques FG, Rodriguez JL: Tolerability of leukotriene modifiers in asthma: a review of clinical experience. BioDrugs. 1999 Jun;11(6):385-94. doi: 10.2165/00063030-199911060-00003. [Article]

Enzymes

Details
1. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Dekhuijzen PN, Koopmans PP: Pharmacokinetic profile of zafirlukast. Clin Pharmacokinet. 2002;41(2):105-14. doi: 10.2165/00003088-200241020-00003. [Article]
  3. Lee HJ, Kim YH, Kim SH, Lee CM, Yang AY, Jang CG, Lee SY, Bae JW, Choi CI: Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of zafirlukast. Arch Pharm Res. 2016 Jul;39(7):1013-9. doi: 10.1007/s12272-016-0785-x. Epub 2016 Jul 4. [Article]
  4. Flockhart Table of Drug Interactions [Link]
  5. Zafirlukast FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
The clinical significance of these enzyme actions in vivo are unknown, and these listed enzyme actions are based on the results of in vitro studies.
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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [Article]
  2. Jaakkola T, Backman JT, Neuvonen M, Niemi M, Neuvonen PJ: Montelukast and zafirlukast do not affect the pharmacokinetics of the CYP2C8 substrate pioglitazone. Eur J Clin Pharmacol. 2006 Jul;62(7):503-9. doi: 10.1007/s00228-006-0136-9. Epub 2006 May 3. [Article]
  3. Jaakkola T, Laitila J, Neuvonen PJ, Backman JT: Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol. 2006 Jul;99(1):44-51. doi: 10.1111/j.1742-7843.2006.pto_437.x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Garey KW, Peloquin CA, Godo PG, Nafziger AN, Amsden GW: Lack of effect of zafirlukast on the pharmacokinetics of azithromycin, clarithromycin, and 14-hydroxyclarithromycin in healthy volunteers. Antimicrob Agents Chemother. 1999 May;43(5):1152-5. [Article]
  2. Kassahun K, Skordos K, McIntosh I, Slaughter D, Doss GA, Baillie TA, Yost GS: Zafirlukast metabolism by cytochrome P450 3A4 produces an electrophilic alpha,beta-unsaturated iminium species that results in the selective mechanism-based inactivation of the enzyme. Chem Res Toxicol. 2005 Sep;18(9):1427-37. doi: 10.1021/tx050092b. [Article]
  3. Karonen T, Laitila J, Niemi M, Neuvonen PJ, Backman JT: Fluconazole but not the CYP3A4 inhibitor, itraconazole, increases zafirlukast plasma concentrations. Eur J Clin Pharmacol. 2012 May;68(5):681-8. doi: 10.1007/s00228-011-1158-5. Epub 2011 Nov 23. [Article]
  4. Liu KH, Lee YM, Shon JH, Kim MJ, Lee SS, Yoon YR, Cha IJ, Shin JG: Potential of pranlukast and zafirlukast in the inhibition of human liver cytochrome P450 enzymes. Xenobiotica. 2004 May;34(5):429-38. doi: 10.1080/00498250410001691253 . [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data is limited to in vitro studies.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Shader RI, Granda BW, von Moltke LL, Giancarlo GM, Greenblatt DJ: Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast. Biopharm Drug Dispos. 1999 Nov;20(8):385-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data supporting this enzyme inhibition is limited to one in vitro study.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Shader RI, Granda BW, von Moltke LL, Giancarlo GM, Greenblatt DJ: Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast. Biopharm Drug Dispos. 1999 Nov;20(8):385-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Shader RI, Granda BW, von Moltke LL, Giancarlo GM, Greenblatt DJ: Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast. Biopharm Drug Dispos. 1999 Nov;20(8):385-8. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Sun YL, Kathawala RJ, Singh S, Zheng K, Talele TT, Jiang WQ, Chen ZS: Zafirlukast antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance. Anticancer Drugs. 2012 Sep;23(8):865-73. doi: 10.1097/CAD.0b013e328354a196. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Donkers JM, Zehnder B, van Westen GJP, Kwakkenbos MJ, IJzerman AP, Oude Elferink RPJ, Beuers U, Urban S, van de Graaf SFJ: Reduced hepatitis B and D viral entry using clinically applied drugs as novel inhibitors of the bile acid transporter NTCP. Sci Rep. 2017 Nov 10;7(1):15307. doi: 10.1038/s41598-017-15338-0. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 19, 2024 11:06