Tryptase inhibitors: a novel class of anti-inflammatory drugs.
Tryptase, a serine protease released from mast cell secretory granules, is found at elevated levels in pathophysiologic conditions associated with allergic inflammation. The in vitro and in vivo biological activities of tryptase strongly suggest that tryptase influences lung function, inflammation, matrix degradation, and tissue remodelling. The pathophysiologic role for tryptase in diseases of airway inflammation such as asthma has been confirmed from studies using the selective tryptase inhibitor APC 366 in the allergic sheep model. APC 366 inhibited the allergen-induced early and late airway responses, blocked postchallenge airway hyperresponsiveness, and reduced airway inflammation. A pilot clinical trial with mild to moderate asthmatics also showed that APC 366 protected against allergen-induced early and late responses and reduced airway hyperresponsiveness. Current data provide compelling evidence that tryptase plays a fundamental role in allergic inflammation, and selective tryptase inhibitors may represent a novel class of anti-inflammatory therapeutics for treating asthma and other mast cell-mediated diseases.
Department of Pharmacology, Arris Pharmaceutical, 180 Kimball Way, South San Francisco, California 94080, USA.
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Numerof
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Simpson
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Tanaka