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Arthritis Rheum. 2012;64:S701–2.”
“Introduction Enzymes that cleave peptide bonds in proteins are also known as proteases, proteinases, peptidases, or proteolytic enzymes [1], and function to accelerate the rate of specific biologic reactions by lowering the activation energy of the reaction [2]. selleck kinase inhibitor proteases are eFT-508 most often assumed only to be involved in processes relating to digestion, but the fact that over 2% of the human genome encodes protease genes suggests that they play more

complex functions than digestion alone [3]. Indeed, proteases have been shown to be involved in the regulation of a number of cellular components from growth factors to receptors, as well as processes including immunity, complement cascades, and blood A-769662 mouse coagulation [3]. In addition to involvement in homeostatic processes, increased or dysregulated activity of proteases has been implicated in cancer via its link with tumor growth and invasion [4]. Briefly, proteases are initially produced as inactive precursors, or zymogens, and are distributed in specific organs or locations, where they have little catalytic ability until they are activated by proteolytic cleavage [5]. Further posttranslational mechanisms to control the activity of proteases include phosphorylation, cofactor binding, and segregation of enzyme and/or substrate in vesicles or granules. In addition, the effective concentration AZD9291 in vivo of active enzyme can also be strictly regulated by protease inhibitors, which can reduce functional efficacy

by forming a complex with the protease and effectively “balance” proteolytic activity [6]. In this short review, the therapeutic uses and future outlook for proteases (notably cold-adapted proteases) will be discussed. Therapeutic Use of Proteases Proteases have been used in medicine for several decades and are an established and well tolerated class of therapeutic agent [3]. Early documented use of proteases in the published literature appeared over 100 years ago [7–9]. In general, proteases have been used therapeutically in four areas: the management of gastrointestinal disorders with orally administered agents, as anti-inflammatory agents, as thrombolytic agents for thromboembolic disorders, and as locally administered agents for wound debridement [10]. Since the first approval of a protease drug in 1978 (urokinase, a serine protease indicated for thrombolysis and catheter clearing), a further 11 drugs have been approved for therapeutic use by the US Food and Drug Administration (FDA) [3].