Targeting leukotriene B4in inflammation
| Autor: | Antonio Di Gennaro, Jesper Z. Haeggström |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Leukotriene B4
Clinical Biochemistry Inflammation Pharmacology Proinflammatory cytokine Leukotriene-A4 hydrolase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery Humans Medicine 030304 developmental biology 0303 health sciences Leukotriene Arachidonate 5-Lipoxygenase biology business.industry Leukotriene B4 receptor Lipid signaling 3. Good health chemistry 030220 oncology & carcinogenesis Arachidonate 5-lipoxygenase Immunology biology.protein Molecular Medicine medicine.symptom business |
| Zdroj: | Expert Opinion on Therapeutic Targets Expert Opinion on Therapeutic Targets; Vol 18 |
| ISSN: | 1744-7631 1472-8222 |
| Popis: | Leukotriene (LT) B(4) is a powerful proinflammatory lipid mediator and triggers adherence to the endothelium, activates and recruits leukocytes to the site of injury. When formed in excess, LTB(4) plays a pathogenic role and may sustain chronic inflammation in diseases such as asthma, rheumatoid arthritis, and inflammatory bowel disease. Recent investigations have also indicated that LTB(4) is involved in cardiovascular diseases.As the 5-lipoxygenase pathway involves several discrete, tightly coupled, enzymes, which convert the substrate, 'step by step', into bioactive products, several different strategies have been used to target LTB(4) as a means to treat inflammation. Here, we discuss recent findings regarding the development of selective enzyme inhibitors and antagonists for LTB(4) receptors, as well as their application in preclinical and clinical studies.Components of the 5-lipoxygenase pathway have received considerable attention as candidate drug targets resulting in one new class of medications against asthma, that is, the antileukotrienes. However, efforts to specifically target LTB(4) have not yet been fruitful in the clinical setting, in spite of very promising preclinical data. Recently, crystal structures along with hitherto unknown functions of key enzymes in the leukotriene cascade have emerged, offering new opportunities for drug development and, with time, pharmacological intervention in LTB(4)-mediated pathologies. |
| Databáze: | OpenAIRE |
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