Zileuton

Identification

Summary

Zileuton is a leukotriene synthesis inhibitor used in the prophylaxis and treatment of chronic asthma.

Brand Names
Zyflo
Generic Name
Zileuton
DrugBank Accession Number
DB00744
Background

Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton relieves such symptoms through its selective inhibition of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it inhibits leukotriene LTB4, LTC4, LTD4, and LTE4 formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. The immediate release tablet of Zileuton has been withdrawn from the US market.

Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Structure
Weight
Average: 236.29
Monoisotopic: 236.061948328
Chemical Formula
C11H12N2O2S
Synonyms
  • (±)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea
  • Leutrol
  • N-(1-Benzo(b)thien-2-ylethyl)-N-hydroxyurea
  • N-[1-(benzo[b]thiophen-2-yl)ethyl]-N-hydroxyurea
  • Zileuton
  • Zileutón
  • Zileutonum
External IDs
  • A 64077

Pharmacology

Indication

For the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.

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
Prevention ofAsthma••••••••••••
Management ofChronic asthma••••••••••••
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

Zileuton is an asthma drug that differs chemically and pharmacologically from other antiasthmatic agents. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. Current data indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4), and can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma.

Mechanism of action

Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Zileuton relieves such symptoms through its selective inhibition of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. Specifically, it inhibits leukotriene LTB4, LTC4, LTD4, and LTE4 formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. Due to the role of leukotrienes in the pathogenesis of asthma, modulation of leukotriene formation by interruption of 5-lipoxygenase activity may reduce airway symptoms, decrease bronchial smooth muscle tone, and improve asthma control.

TargetActionsOrganism
AArachidonate 5-lipoxygenase
inhibitor
Humans
Absorption

Rapidly and almost completely absorbed. The absolute bioavailability is unknown.

Volume of distribution
  • 1.2 L/kg
Protein binding

93% bound to plasma proteins, primarily to albumin.

Metabolism

Hepatic. Zileuton and its N-dehydroxylated metabolite are oxidatively metabolized by the cytochrome P450 isoenzymes 1A2, 2C9 and 3A4.

Hover over products below to view reaction partners

Route of elimination

Elimination of zileuton is predominantly via metabolism with a mean terminal half-life of 2.5 hours. The urinary excretion of the inactive N-dehydroxylated metabolite and unchanged zileuton each accounted for less than 0.5% of the dose.

Half-life

2.5 hours

Clearance
  • Apparent oral cl=7 mL/min/kg
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

Minimum oral lethal dose of zileuton in various preparations was 500-4000 mg/kg in mice and 300-1000 mg/kg in rats (providing greater than 3 and 9 times the systemic exposure [AUC] achieved at the maximum recommended human daily oral dose, respectively).

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
AbametapirThe serum concentration of Zileuton can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Zileuton can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Zileuton can be increased when it is combined with Abiraterone.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Zileuton.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Zileuton.
Food Interactions
  • Avoid excessive or chronic alcohol consumption.
  • Exercise caution with grapefruit products. Zileuton is partially metabolized through CYP3A4. Therefore grapefruit, a CYP3A4 inhibitor, may reduce the metabolism of zileuton.
  • Exercise caution with St. John's Wort. Zileuton is partially metabolized through CYP3A4. Therefore St. John's Wort may increase the metabolism of zileuton.
  • Take with food. The AUC and Cmin of zileuton extended-release tablets are increased by food, and therefore should be taken with meals.
  • Take with or without food. ZYFLO (zileuton) regular release tablets can be taken with or without food.

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
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ZyfloTablet, film coated600 mg/1OralCritical Therapeutics, Inc.1996-12-092010-08-31US flag
ZyfloTablet600 mg/1OralChiesi USA, Inc.1996-12-06Not applicableUS flag
Zyflo CRTablet, multilayer, extended release600 mg/1OralCritical Therapeutics, Inc.2007-05-302010-12-01US flag
Zyflo CRTablet, multilayer, extended release600 mg/1OralChiesi USA, Inc.2007-05-302019-12-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ZileutonTablet, multilayer, extended release600 mg/1OralPar Pharmaceutical, Inc.2020-01-092023-11-30US flag
ZileutonTablet600 mg/1OralAristos Phamaceuticals, Inc.2016-03-012017-04-10US flag
ZileutonTablet, multilayer, extended release600 mg/1OralDash Pharmaceutical LLC2020-10-23Not applicableUS flag
ZileutonTablet, extended release600 mg/1OralPrasco, Llc2017-03-292023-03-01US flag
ZileutonTablet, extended release600 mg/1OralAristos Phamaceuticals, Inc.2016-11-302017-05-01US flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 1-benzothiophenes. These are aromatic heterocyclic compound containing the Benzo[b]thiophene ring system.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiophenes
Sub Class
1-benzothiophenes
Direct Parent
1-benzothiophenes
Alternative Parents
2,3,5-trisubstituted thiophenes / Benzenoids / Heteroaromatic compounds / Organic carbonic acids and derivatives / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
1-benzothiophene / 2,3,5-trisubstituted thiophene / Aromatic heteropolycyclic compound / Benzenoid / Carbonic acid derivative / Carbonyl group / Heteroaromatic compound / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
ureas, 1-benzothiophenes (CHEBI:10112)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
V1L22WVE2S
CAS number
111406-87-2
InChI Key
MWLSOWXNZPKENC-UHFFFAOYSA-N
InChI
InChI=1S/C11H12N2O2S/c1-7(13(15)11(12)14)10-6-8-4-2-3-5-9(8)16-10/h2-7,15H,1H3,(H2,12,14)
IUPAC Name
1-[1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea
SMILES
CC(N(O)C(N)=O)C1=CC2=CC=CC=C2S1

References

Synthesis Reference

Emanuele ATTOLINA, Gianmaria Dell'Anna, Roberto Rossi, Pietro Allegrini, Gabriele Razzetti, "PROCESS FOR THE PREPARATION OF ZILEUTON." U.S. Patent US20090286996, issued November 19, 2009.

US20090286996
General References
  1. Berger W, De Chandt MT, Cairns CB: Zileuton: clinical implications of 5-Lipoxygenase inhibition in severe airway disease. Int J Clin Pract. 2007 Apr;61(4):663-76. [Article]
  2. Wenzel SE, Kamada AK: Zileuton: the first 5-lipoxygenase inhibitor for the treatment of asthma. Ann Pharmacother. 1996 Jul-Aug;30(7-8):858-64. [Article]
  3. Malo PE, Bell RL, Shaughnessy TK, Summers JB, Brooks DW, Carter GW: The 5-lipoxygenase inhibitory activity of zileuton in in vitro and in vivo models of antigen-induced airway anaphylaxis. Pulm Pharmacol. 1994 Apr;7(2):73-9. [Article]
Human Metabolome Database
HMDB0014882
KEGG Drug
D00414
PubChem Compound
60490
PubChem Substance
46506394
ChemSpider
54531
BindingDB
50000541
RxNav
40575
ChEBI
10112
ChEMBL
CHEMBL93
Therapeutic Targets Database
DAP000591
PharmGKB
PA451955
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Zileuton
FDA label
Download (129 KB)
MSDS
Download (14.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAsthma2
4RecruitingTreatmentTrigeminal Neuralgia (TN)1
4TerminatedTreatmentAsthma1
3TerminatedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
2CompletedPreventionHead And Neck Cancer / Lung Cancer1

Pharmacoeconomics

Manufacturers
  • Cornerstone therapeutics inc
Packagers
  • Cornerstone Pharmacy
  • Critical Therapeutics Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Patheon Inc.
Dosage Forms
FormRouteStrength
PowderNot applicable1 kg/1kg
TabletOral600 mg/1
Tablet, extended releaseOral600 1/1
Tablet, extended releaseOral600 mg/1
Tablet, film coated, extended releaseOral600 mg/1
Tablet, film coatedOral600 mg/1
Tablet, multilayer, extended releaseOral600 mg/1
Prices
Unit descriptionCostUnit
Zyflo 600 mg tablet6.49USD tablet
Zyflo CR 600 mg 12 Hour tablet6.23USD tablet
Zyflo 600 mg filmtab5.99USD tablet
Zyflo cr 600 mg tablet5.99USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5422123No1995-06-062012-06-06US flag
US4873259No1989-10-102010-12-09US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)144.2-145.2 °CNot Available
water solubilityPractically insoluble (0.5 mg/ml)Not Available
logP0.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0539 mg/mLALOGPS
logP2.01ALOGPS
logP2.01Chemaxon
logS-3.6ALOGPS
pKa (Strongest Acidic)8.84Chemaxon
pKa (Strongest Basic)-5.5Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area66.56 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity61.96 m3·mol-1Chemaxon
Polarizability24.14 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9915
Blood Brain Barrier+0.8846
Caco-2 permeable-0.5793
P-glycoprotein substrateNon-substrate0.6789
P-glycoprotein inhibitor INon-inhibitor0.9684
P-glycoprotein inhibitor IINon-inhibitor0.9765
Renal organic cation transporterNon-inhibitor0.9583
CYP450 2C9 substrateNon-substrate0.5907
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6384
CYP450 1A2 substrateInhibitor0.5318
CYP450 2C9 inhibitorNon-inhibitor0.7975
CYP450 2D6 inhibitorNon-inhibitor0.8866
CYP450 2C19 inhibitorNon-inhibitor0.6451
CYP450 3A4 inhibitorNon-inhibitor0.7062
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5821
Ames testAMES toxic0.5865
CarcinogenicityNon-carcinogens0.7968
BiodegradationNot ready biodegradable0.985
Rat acute toxicity2.2646 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9884
hERG inhibition (predictor II)Non-inhibitor0.9051
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-MSsplash10-01ox-5900000000-908922c27d630436d92c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-01p9-0970000000-61a67ba9d485fc7ac2a5
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9200000000-da750f8c445111ce6d3f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0900000000-482e8faeca8ed7253b6a
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-06sl-8900000000-9210677ae4daee909638
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0bt9-2900000000-15a6d0d70b01c366f6be
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-4900000000-1df9e010d335b35e9ead
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-157.852736
predicted
DarkChem Lite v0.1.0
[M-H]-141.54823
predicted
DeepCCS 1.0 (2019)
[M+H]+159.672536
predicted
DarkChem Lite v0.1.0
[M+H]+143.90623
predicted
DeepCCS 1.0 (2019)
[M+Na]+159.011936
predicted
DarkChem Lite v0.1.0
[M+Na]+150.59766
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
Inhibitor
General Function
Iron ion binding
Specific Function
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name
ALOX5
Uniprot ID
P09917
Uniprot Name
Arachidonate 5-lipoxygenase
Molecular Weight
77982.595 Da
References
  1. Wenzel SE: Leukotriene receptor antagonists and related compounds. Can Respir J. 1999 Mar-Apr;6(2):189-93. [Article]
  2. Hardy DB, Pereria LE, Yang K: Prostaglandins and leukotriene B4 are potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 2 activity in human choriocarcinoma JEG-3 cells. Biol Reprod. 1999 Jul;61(1):40-5. [Article]
  3. Yamashita M, Kushihara M, Hirasawa N, Takasaki W, Takahagi H, Takayanagi M, Ohuchi K: Inhibition by troglitazone of the antigen-induced production of leukotrienes in immunoglobulin E-sensitized RBL-2H3 cells. Br J Pharmacol. 2000 Jan;129(2):367-73. [Article]
  4. Qian C, Hwang SB, Libertine-Garahan L, Eckman JB, Cai X, Scannell RT, Yeh CG: Anti-inflammatory activities of LDP-392, a dual PAF receptor antagonist and 5-lipoxygenase inhibitor. Pharmacol Res. 2001 Sep;44(3):213-20. [Article]
  5. Coffey MJ, Phare SM, Peters-Golden M: Peroxynitrite-induced nitrotyrosination of proteins is blocked by direct 5-lipoxygenase inhibitor zileuton. J Pharmacol Exp Ther. 2001 Oct;299(1):198-203. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. Zouboulis CC: Zileuton, a new efficient and safe systemic anti-acne drug. Dermatoendocrinol. 2009 May;1(3):188-92. [Article]
  8. Zouboulis CC, Seltmann H, Alestas T: Zileuton prevents the activation of the leukotriene pathway and reduces sebaceous lipogenesis. Exp Dermatol. 2010 Feb;19(2):148-50. doi: 10.1111/j.1600-0625.2009.00929.x. Epub 2009 Jul 23. [Article]
  9. Berger W, De Chandt MT, Cairns CB: Zileuton: clinical implications of 5-Lipoxygenase inhibition in severe airway disease. Int J Clin Pract. 2007 Apr;61(4):663-76. [Article]
  10. Guidot DM, Repine MJ, Westcott JY, Repine JE: Intrinsic 5-lipoxygenase activity is required for neutrophil responsivity. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8156-9. [Article]
  11. Wenzel SE, Kamada AK: Zileuton: the first 5-lipoxygenase inhibitor for the treatment of asthma. Ann Pharmacother. 1996 Jul-Aug;30(7-8):858-64. [Article]
  12. Tanaka R: [5-lipoxygenase inhibitors in asthma therapy]. Nihon Rinsho. 1996 Nov;54(11):3040-4. [Article]
  13. 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]
  14. Chen HC, Xie J, Zhang Z, Su LT, Yue L, Runnels LW: Blockade of TRPM7 channel activity and cell death by inhibitors of 5-lipoxygenase. PLoS One. 2010 Jun 17;5(6):e11161. doi: 10.1371/journal.pone.0011161. [Article]

Enzymes

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
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 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
Curator comments
The FDA label indicates that this enzyme action is supported only by the findings 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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Machinist JM, Mayer MD, Shet MS, Ferrero JL, Rodrigues AD: Identification of the human liver cytochrome P450 enzymes involved in the metabolism of zileuton (ABT-077) and its N-dehydroxylated metabolite, Abbott-66193. Drug Metab Dispos. 1995 Oct;23(10):1163-74. [Article]
  2. Zileuton FDA [File]
Details
4. Cytochrome P450 1A2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [Article]
  2. 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]
  3. Machinist JM, Mayer MD, Shet MS, Ferrero JL, Rodrigues AD: Identification of the human liver cytochrome P450 enzymes involved in the metabolism of zileuton (ABT-077) and its N-dehydroxylated metabolite, Abbott-66193. Drug Metab Dispos. 1995 Oct;23(10):1163-74. [Article]
  4. Flockhart Table of Drug Interactions [Link]
  5. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  6. Zileuton FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
The clinical significance of this drug interacting with CYP3A4 substrates is undetermined at this time, according to prescribing information.
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. 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. Machinist JM, Mayer MD, Shet MS, Ferrero JL, Rodrigues AD: Identification of the human liver cytochrome P450 enzymes involved in the metabolism of zileuton (ABT-077) and its N-dehydroxylated metabolite, Abbott-66193. Drug Metab Dispos. 1995 Oct;23(10):1163-74. [Article]
  3. FDA Approved Drug Products: ZYFLO CR (zileuton) extended-release tablets [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Li F, Chordia MD, Woodling KA, Macdonald TL: Irreversible alkylation of human serum albumin by zileuton metabolite 2-acetylbenzothiophene-S-oxide: a potential model for hepatotoxicity. Chem Res Toxicol. 2007 Dec;20(12):1854-61. Epub 2007 Oct 19. [Article]

Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 06:55