Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications.
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April 2011
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Review Article|
March 15 2011
Proteases as therapeutics
Charles S. Craik;
Charles S. Craik
1
*Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94131, U.S.A.
1To whom correspondence should be addressed (email craik@cgl.ucsf.edu).
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Michael J. Page;
Michael J. Page
*Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94131, U.S.A.
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Edwin L. Madison
Edwin L. Madison
†Catalyst Biosciences, 260 Littlefield Avenue, South San Francisco, CA 94080, U.S.A.
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Publisher: Portland Press Ltd
Received:
July 15 2010
Revision Received:
December 10 2010
Accepted:
December 10 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 435 (1): 1–16.
Article history
Received:
July 15 2010
Revision Received:
December 10 2010
Accepted:
December 10 2010
Citation
Charles S. Craik, Michael J. Page, Edwin L. Madison; Proteases as therapeutics. Biochem J 1 April 2011; 435 (1): 1–16. doi: https://doi.org/10.1042/BJ20100965
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