Identification of an Orally Efficacious Matrix Metalloprotease 12 Inhibitor for Potential Treatment of Asthma
Journal of Medicinal Chemistry2009Vol. 52(17), pp. 5408–5419
Citations Over TimeTop 17% of 2009 papers
Wei Li, Jianchang Li, Yuchuan Wu, Fabio Rancati, Stefania Vallese, Luca F. Raveglia, Junjun Wu, Rajeev Hotchandani, Nathan O. Fuller, Kristina Cunningham, Paul Morgan, Susan Fish, Rustem Krykbaev, Xin Xu, Steve Tam, Samuel J. Goldman, William Abraham, Cara Williams, Joseph P. Sypek, Tarek S. Mansour
Abstract
MMP-12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been observed in the lungs of asthmatic patients. Compound 27 was identified as a potent and selective MMP-12 inhibitor possessing good physicochemical properties. In pharmacological studies, the compound was orally efficacious in an MMP-12 induced ear-swelling inflammation model in the mouse with a good dose response. This compound also exhibited oral efficacy in a naturally Ascaris-sensitized sheep asthma model showing significant inhibition of the late phase response to allergen challenge. This compound has been considered for further development as a treatment therapy for asthma.
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