Journal ArticleDOI
Targeting proteases: successes, failures and future prospects.
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TLDR
The status of human protease research and prospects for future protease-targeted drugs are reviewed, with reference to some key examples where protease drugs have succeeded or failed.Abstract:
Far from being simple degradative enzymes, proteases are now seen as key signalling molecules and desirable drug targets in several diseases. Turk discusses our success so far at targeting proteases and how these enzymes might be exploited therapeutically in the future. Until fairly recently, proteases were considered primarily to be protein-degrading enzymes. However, this view has dramatically changed and proteases are now seen as extremely important signalling molecules that are involved in numerous vital processes. Protease signalling pathways are strictly regulated, and the dysregulation of protease activity can lead to pathologies such as cardiovascular and inflammatory diseases, cancer, osteoporosis and neurological disorders. Several small-molecule drugs targeting proteases are already on the market and many more are in development. The status of human protease research and prospects for future protease-targeted drugs are reviewed here, with reference to some key examples where protease drugs have succeeded or failed.read more
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Cysteine cathepsins: From structure, function and regulation to new frontiers
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References
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Journal ArticleDOI
On the size of the active site in proteases. I. Papain.
Israel Schechter,Arieh Berger +1 more
Journal ArticleDOI
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction
TL;DR: It is clear now that degradation of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a variety of basic pathways during cell life and death as well as in health and disease.
Journal ArticleDOI
A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
Masato Enari,Hideki Sakahira,Hideki Yokoyama,Katsuya Okawa,Akihiro Iwamatsu,Shigekazu Nagata,Shigekazu Nagata +6 more
TL;DR: A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells and seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity.
Journal ArticleDOI
Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations
TL;DR: The studies that brought MPIs into clinical testing are reviewed and the design and outcome of the trials are discussed in light of new information about the cellular source, substrates, and mode of action of MMPs at different stages of tumor progression.
Journal ArticleDOI
A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.
Nancy A. Thornberry,Herbert G. Bull,Jimmy R. Calaycay,Kevin T. Chapman,Andrew D. Howard,Matthew J. Kostura,Douglas K. Miller,Susan M. Molineaux,Jeffrey R. Weidner,John G. Aunins,Keith O. Elliston,Julia M. Ayala,Francesca J. Casano,Jayne Chin,Gloria J.-F. Ding,Linda A. Egger,Erin P. Gaffney,Guadalupe A. Limjuco,Oksana C. Palyha,S.M. Raju,Anna M. Rolando,J. Paul Salley,Ting-Ting Yamin,Terry D. Lee,John E. Shively,Malcolm MacCross,Richard A. Mumford,John A. Schmidt,Michael J. Tocci +28 more
TL;DR: Purification and cloning of the complementary DNA indicates that IL-lβ-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis.