| Candidate ID: | R0263 |
| Source ID: | DB00744 |
| Source Type: | approved; investigational; withdrawn |
| Compound Type: |
small molecule
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| Compound Name: |
Zileuton
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| 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
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| Molecular Formula: |
C11H12N2O2S
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| SMILES: |
CC(N(O)C(N)=O)C1=CC2=CC=CC=C2S1
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| Structure: |
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| DrugBank Description: |
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 The immediate release tablet of Zileuton has been withdrawn from the US market.
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| CAS Number: |
111406-87-2
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| Molecular Weight: |
236.29
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| DrugBank Indication: |
For the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.
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| DrugBank Pharmacology: |
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.
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| DrugBank MoA: |
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 <i>in vitro</i> 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.
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| Targets: |
Arachidonate 5-lipoxygenase inhibitor
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| Inclusion Criteria: |
Therapeutic strategy associated
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