期刊
PROTEOMICS
卷 17, 期 23-24, 页码 -出版社
WILEY
DOI: 10.1002/pmic.201600389
关键词
cancer; colitis; clinical trial; inflammation; metalloproteinase; protease inhibitor
资金
- State of Florida
- Executive Office of the Governor's Office of Tourism, Trade, and Economic Development [2KN05]
- Office of Vice President for Research of Auburn University
- National Institutes of Health [CA98799, AR063795, MH078948]
- National Institutes of Health (NHLBI) [268201000036C, DA033985, AR066676]
- Multiple Sclerosis National Research Institute
- Robert A. Welch Foundation
- Lustgarten Foundation
Remodeling of the extracellular matrix (ECM) is crucial in development and homeostasis, but also has a significant role in disease progression. Two metalloproteinase families, the matrix metalloproteinases (MMPs) and a disintegrin and metalloproteases (ADAMs), participate in the remodeling of the ECM, either directly or through the liberation of growth factors and cell surface receptors. The correlation of MMP and ADAM activity to a variety of diseases has instigated numerous drug development programs. However, broad-based and Zn2+-chelating MMP and ADAM inhibitors have fared poorly in the clinic. Selective MMP and ADAM inhibitors have been described recently based on (a) antibodies or antibody fragments or (b) small molecules designed to take advantage of protease secondary binding sites (exosites) or allosteric sites. Clinical trials have been undertaken with several of these inhibitors, while others are in advanced pre-clinical stages.
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