Proteases as therapeutics

By C. Craik, Michael J. Page, E. Madison. 2011

220 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Hematology, Physiology

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In Cancer Research

1. David R. Liu
2. M. Packer
3. H. Rees

In Hematology

1. David R. Liu
2. M. Packer
3. H. Rees

In Physiology

1. David R. Liu
2. M. Packer
3. H. Rees

Citations in the corpus

• Phage-assisted continuous evolution of proteases with altered substrate specificity (2017, methodology): “In order to evolve high levels of activity on the final target substrate from these weakly active mutants, we applied three strategies to increase selection stringency on all three trajectories: (1) express a lower concentration of the PA-RNAP substrate by using a weaker constitutive promoter (proA ”