Details
Stereochemistry | RACEMIC |
Molecular Formula | C11H12N2O2S |
Molecular Weight | 236.2917 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(c1cc2ccccc2s1)N(C(=N)O)O
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)
Molecular Formula | C11H12N2O2S |
Molecular Weight | 236.2917 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
0.3 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ZYFLO Approved UseZYFLO is indicated for the prophylaxis and chronic treatment of asthma in adults and
children 12 years of age and older. Launch Date8.5000323E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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%) Sources: Page: p.846ALT increased (2.7%) Asthma (3.7%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
Title | Date | PubMed |
---|---|---|
Inhibition of 5-LO activating protein (FLAP) activity decreases proteinuria in streptozotocin (STZ)-induced diabetic rats. | 2002 |
|
Effects of Celebrex and Zyflo on liver metastasis and lipidperoxidation in pancreatic cancer in Syrian hamsters. | 2002 |
|
Leukotrienes antagonists in the management of bronchial asthma. | 2003 |
|
Recent advances in the management of asthma using leukotriene modifiers. | 2003 |
|
Benefit-risk assessment of antileukotrienes in the management of asthma. | 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 |
|
Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer. | 2003 Jan 7 |
|
Inhibition of 5-lipoxygenase activating protein decreases proteinuria in diabetic rats. | 2003 Jan-Feb |
|
[Anti-leukotrienes in allergic diseases in children]. | 2003 Jun |
|
The role of leukotriene inhibitors in patients with paranasal sinus disease. | 2003 Jun |
|
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 |
|
Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. | 2003 Nov |
|
Inhibition of neutrophil leukotriene B4 production by a novel synthetic N-3 polyunsaturated fatty acid analogue, beta-oxa 21:3n-3. | 2003 Nov 1 |
|
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia. | 2003 Nov 17 |
|
Deficiency of NADPH oxidase components p47phox and gp91phox caused granulomatous synovitis and increased connective tissue destruction in experimental arthritis models. | 2003 Oct |
|
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 |
|
Zileuton, a 5-lipoxygenase inhibitor, increases production of thromboxane A2 and platelet aggregation in patients with asthma. | 2003 Sep |
|
Tenofovir, COX inhibitors and zileuton during cancer immunotherapies: up-regulated TNF-alpha increases antigen driven lymphocyte proliferation. | 2003 Sep |
|
Effect of zileuton in radicular pain induced by herniated nucleus pulposus in rats. | 2004 |
|
Idiopathic pulmonary fibrosis: pathogenesis and therapeutic approaches. | 2004 |
|
Reduction of renal ischemia-reperfusion injury in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton. | 2004 Aug |
|
Involvement of mast cells in basal and neurotensin-induced intestinal absorption of taurocholate in rats. | 2004 Aug |
|
Advances in therapy with antileukotriene drugs. | 2004 Autumn |
|
In vitro metabolism of 2-acetylbenzothiophene: relevance to zileuton hepatotoxicity. | 2004 Feb |
|
Effect of 5-lipoxygenase inhibition on events associated with inflammatory bowel disease in rats. | 2004 Jul |
|
Suppression of leukotriene B4 generation by ex-vivo neutrophils isolated from asthma patients on dietary supplementation with gammalinolenic acid-containing borage oil: possible implication in asthma. | 2004 Mar |
|
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 |
|
Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats. | 2004 May |
|
Zileuton induces hemoglobin F synthesis in erythroid progenitors: role of the L-arginine-nitric oxide signaling pathway. | 2004 May 15 |
|
Anti-proliferative effects of lichen-derived lipoxygenase inhibitors on twelve human cancer cell lines of different tissue origin in vitro. | 2004 Nov |
|
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 |
|
Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. | 2004 Nov 15 |
|
The improved survival of experimental animals fed with fish oil is suppressed by a leukotriene inhibitor. | 2004 Oct |
|
Overexpression of 5-lipoxygenase in rat and human esophageal adenocarcinoma and inhibitory effects of zileuton and celecoxib on carcinogenesis. | 2004 Oct 1 |
|
Modulation of pulmonary leukotriene B4 production by cyclooxygenase-2 inhibitors and lipopolysaccharide. | 2004 Oct 15 |
|
Aspirin-triggered, cyclooxygenase-2-dependent lipoxin synthesis modulates vascular tone. | 2004 Sep 7 |
|
Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production. | 2005 |
|
The effects of a 5-lipoxygenase inhibitor on acute mountain sickness and urinary leukotriene e4 after ascent to high altitude. | 2005 Feb |
|
Asthma controller therapy during pregnancy. | 2005 Feb |
|
Leukotrienes: their role in the treatment of asthma and seasonal allergic rhinitis. | 2005 Jan-Feb |
|
5-Lipoxygenase modulates colitis through the regulation of adhesion molecule expression and neutrophil migration. | 2005 Jun |
|
Correlation of in vitro chemopreventive efficacy data from the human epidermal cell assay with animal efficacy data and clinical trial plasma levels. | 2005 Jun 1 |
|
Overexpression of 5-lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib. | 2005 Mar 1 |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10319915
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
Edited
Fri Jun 25 20:33:10 UTC 2021
by
admin
on
Fri Jun 25 20:33:10 UTC 2021
|
Record UNII |
V1L22WVE2S
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NDF-RT |
N0000008683
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
||
|
NDF-RT |
N0000175956
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
||
|
LIVERTOX |
1048
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
||
|
NCI_THESAURUS |
C1322
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
||
|
NDF-RT |
N0000175955
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
||
|
NDF-RT |
N0000008683
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
DB00744
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
CHEMBL93
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
111406-87-2
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
6595
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
C26667
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
Zileuton
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
C063449
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
1724656
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | USP-RS | ||
|
ZILEUTON
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
60490
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
SUB00157MIG
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
111406-87-2
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
40575
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | RxNorm | ||
|
V1L22WVE2S
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
M11593
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | Merck Index | ||
|
5297
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
PRIMARY | |||
|
2862
Created by
admin on Fri Jun 25 20:33:10 UTC 2021 , Edited by admin on Fri Jun 25 20:33:10 UTC 2021
|
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 | ||
---|---|---|---|---|
|
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 |
|
||
Route of Elimination | PHARMACOKINETIC |
|