Identification of an orally efficacious matrix metalloprotease 12 inhibitor for potential treatment of asthma.

Full 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.

Author information

Author/s: Li, Wei (W); Li, Jianchang (J); Wu, Yuchuan (Y); Rancati, Fabio (F); Vallese, Stefania (S); Raveglia, Luca (L); Wu, Junjun (J); Hotchandani, Rajeev (R); Fuller, Nathan (N); Cunningham, Kristina (K); Morgan, Paul (P); Fish, Susan (S); Krykbaev, Rustem (R); Xu, Xin (X); Tam, Steve (S); Goldman, Samuel J (SJ); Abraham, William (W); Williams, Cara (C); Sypek, Joseph (J); Mansour, Tarek S (TS);

Affiliation: Chemical Sciences, Wyeth Research, Cambridge, Massachusetts 02140, USA. weili(-atsign-)wyeth.com

Journal and publication information

Publication Type: Journal Article

Journal: Journal of medicinal chemistry (J Med Chem), published in United States. (Language: eng)

Reference: 2009-Sep; vol 52 (issue 17) : pp 5408-19

Dates: Created 2009/09/03; Completed 2009/09/25;

PMID: 19725580, status: MEDLINE (last retrieval date: 9/25/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.