U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C11H12N2O2S
Molecular Weight 236.29
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZILEUTON

SMILES

CC(N(O)C(N)=O)C1=CC2=C(S1)C=CC=C2

InChI

InChIKey=MWLSOWXNZPKENC-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C11H12N2O2S
Molecular Weight 236.29
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment: Description was created based on several sources, including

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. Zileuton is a specific inhibitor of 5-lipoxygenase and thus 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. 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 is marketed under the trade name ZYFLO.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZYFLO

Approved Use

ZYFLO is indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.

Launch Date

1996
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.98 μg/mL
600 mg 4 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ZILEUTON unknown
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
19.2 μg × h/mL
600 mg 4 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ZILEUTON unknown
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
600 mg 4 times / day multiple, oral
Studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources: Page: p.846
unhealthy, ADULT
n = 2458
Health Status: unhealthy
Condition: chronic asthma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2458
Sources: Page: p.846
Disc. AE: Dyspepsia...
Other AEs: Nausea, ALT increased...
AEs leading to
discontinuation/dose reduction:
Dyspepsia (1.6%)
Other AEs:
Nausea (2.4%)
ALT increased (2.7%)
Asthma (3.7%)
Sources: Page: p.846
AEs

AEs

AESignificanceDosePopulation
Dyspepsia 1.6%
Disc. AE
600 mg 4 times / day multiple, oral
Studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources: Page: p.846
unhealthy, ADULT
n = 2458
Health Status: unhealthy
Condition: chronic asthma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2458
Sources: Page: p.846
Nausea 2.4%
600 mg 4 times / day multiple, oral
Studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources: Page: p.846
unhealthy, ADULT
n = 2458
Health Status: unhealthy
Condition: chronic asthma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2458
Sources: Page: p.846
ALT increased 2.7%
600 mg 4 times / day multiple, oral
Studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources: Page: p.846
unhealthy, ADULT
n = 2458
Health Status: unhealthy
Condition: chronic asthma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2458
Sources: Page: p.846
Asthma 3.7%
600 mg 4 times / day multiple, oral
Studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources: Page: p.846
unhealthy, ADULT
n = 2458
Health Status: unhealthy
Condition: chronic asthma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2458
Sources: Page: p.846
PubMed

PubMed

TitleDatePubMed
Anti-inflammatory effects of zileuton in a subpopulation of allergic asthmatics.
2000 Apr
Role of the IgE-mediated system in eosinophil recruitment triggered by two consecutive cycles of sensitisation and challenge in rats.
2001 Dec
ABT-761 (Abbott).
2001 Jan
Discovery of leukotrienes and development of antileukotriene agents.
2001 Jun
The role of antileukotrienes in the treatment of asthma.
2001 Jun
N-Aminoindoline derivatives as inhibitors of 5-lipoxygenase.
2001 Mar 26
Leukotrienes play protective roles early during experimental VSV encephalitis.
2001 Nov 1
[Leukotriene modifiers].
2001 Oct
Peroxynitrite-induced nitrotyrosination of proteins is blocked by direct 5-lipoxygenase inhibitor zileuton.
2001 Oct
Inhibition of 5-LO activating protein (FLAP) activity decreases proteinuria in streptozotocin (STZ)-induced diabetic rats.
2002
Pharmacogenetics, pharmacogenomics and airway disease.
2002
Treatment of disseminated granuloma annulare with a 5-lipoxygenase inhibitor and vitamin E.
2002 Apr
Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase.
2002 Dec 15
[Anti-leukotriene drugs and Churg Strauss syndrome].
2002 Feb
Pharmacological characterization of SC-57461A (3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl), a potent and selective inhibitor of leukotriene A(4) hydrolase II: in vivo studies.
2002 Feb
[New horizons in the treatment of atopic dermatitis].
2002 May-Jun
Mechanisms of idiosyncratic drug reactions: the case of felbamate.
2002 Nov 10
Interaction between nitric oxide, reactive oxygen intermediates, and peroxynitrite in the regulation of 5-lipoxygenase metabolism.
2002 Oct 10
Mediators of adenosine- and ovalbumen-induced bronchoconstriction of sensitized guinea-pig isolated airways.
2002 Sep 6
Recent advances in the management of asthma using leukotriene modifiers.
2003
Leukotrienes mediate murine bronchopulmonary hyperreactivity, inflammation, and part of mucosal metaplasia and tissue injury induced by recombinant murine interleukin-13.
2003 Apr
Anti-leukotriene drugs in the prevention and treatment of hepatorenal syndrome.
2003 Apr
Generalized granuloma annulare in a patient with adult onset diabetes mellitus.
2003 Dec
Leukotrienes, IL-13, and chemokines cooperate to induce BHR and mucus in allergic mouse lungs.
2003 Feb
Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer.
2003 Jan 7
Zileuton reduces respiratory illness and lung inflammation, during respiratory syncytial virus infection, in mice.
2003 Jun 1
Toxicity of human monocytic THP-1 cells and microglia toward SH-SY5Y neuroblastoma cells is reduced by inhibitors of 5-lipoxygenase and its activating protein FLAP.
2003 Mar
A new concept for acne therapy: a pilot study with zileuton, an oral 5-lipoxygenase inhibitor.
2003 May
Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants.
2003 May
Use of a low-density microarray for studying gene expression patterns induced by hepatotoxicants on primary cultures of rat hepatocytes.
2003 Oct
Leukotrienes mediate part of Ova-induced lung effects in mice via EGFR.
2003 Oct
Tenofovir, COX inhibitors and zileuton during cancer immunotherapies: up-regulated TNF-alpha increases antigen driven lymphocyte proliferation.
2003 Sep
Involvement of mast cells in basal and neurotensin-induced intestinal absorption of taurocholate in rats.
2004 Aug
Leukotriene modifier use and asthma severity: how is a new medication being used by adults with asthma?
2004 Mar 22
Evaluation of the utilization patterns of leukotriene modifiers in a large managed care health plan.
2004 Mar-Apr
Zileuton induces hemoglobin F synthesis in erythroid progenitors: role of the L-arginine-nitric oxide signaling pathway.
2004 May 15
Reduction of the multiple organ injury and dysfunction caused by endotoxemia in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton.
2004 Nov
Overexpression of 5-lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib.
2005 Mar 1
Patents

Sample Use Guides

The recommended dosage of ZYFLO (Zileuton) for the symptomatic treatment of patien ts with asthma is one 600-mg tablet four times a day for a total daily dose of 2400 mg. For ease of administration, ZYFLO may be taken with meals and at bedtime.
Route of Administration: Oral
Zileuton (5 uM) inhibited LTB4 production by 99% in purified human neutrophils in the presence of fatty acid saturated albumin (fraction V).
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:53:14 GMT 2023
Edited
by admin
on Fri Dec 15 15:53:14 GMT 2023
Record UNII
V1L22WVE2S
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ZILEUTON
INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
NSC-730712
Code English
(±)-1-(1-BENZO(B)THIEN-2-YLETHYL)-1-HYDROXYUREA
Systematic Name English
UREA, N-(1-BENZO(B)THIEN-2-YLETHYL)-N-HYDROXY-, (±)-
Systematic Name English
ZILEUTON [USAN]
Common Name English
NSC-759277
Code English
ZILEUTON [USP-RS]
Common Name English
zileuton [INN]
Common Name English
ZILEUTON [MI]
Common Name English
ZYFLO
Brand Name English
A-64077
Code English
ZILEUTON [USP MONOGRAPH]
Common Name English
ABBOTT-64077
Code English
ZILEUTON [ORANGE BOOK]
Common Name English
ZILEUTON [MART.]
Common Name English
Zileuton [WHO-DD]
Common Name English
ZILEUTON [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000008683
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
NDF-RT N0000175956
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
LIVERTOX NBK548397
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
NCI_THESAURUS C1322
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
NDF-RT N0000175955
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
NDF-RT N0000008683
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
Code System Code Type Description
NSC
759277
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
DRUG BANK
DB00744
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
NSC
730712
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
ChEMBL
CHEMBL93
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
SMS_ID
100000079065
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
CHEBI
10112
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
USAN
AA-18
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
CAS
111406-87-2
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
INN
6595
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
NCI_THESAURUS
C26667
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
DAILYMED
V1L22WVE2S
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
LACTMED
Zileuton
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
MESH
C063449
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
RS_ITEM_NUM
1724656
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
WIKIPEDIA
ZILEUTON
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
PUBCHEM
60490
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
EVMPD
SUB00157MIG
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
EPA CompTox
DTXSID9023752
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
RXCUI
40575
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY RxNorm
FDA UNII
V1L22WVE2S
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
MERCK INDEX
m11593
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY Merck Index
IUPHAR
5297
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
DRUG CENTRAL
2862
Created by admin on Fri Dec 15 15:53:14 GMT 2023 , Edited by admin on Fri Dec 15 15:53:14 GMT 2023
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
FECAL; URINE
METABOLIC ENZYME -> SUBSTRATE
ENANTIOMER -> RACEMATE
ENANTIOMER -> RACEMATE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
IN-VITRO
METABOLITE -> PARENT
METABOLITE -> PARENT
IN-VITRO
METABOLITE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Route of Elimination PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

FED CONDITION

Route of Elimination PHARMACOKINETIC