Molecular Therapeutics, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom.
Biochimie. 2010 Nov;92(11):1681-8. doi: 10.1016/j.biochi.2010.03.010. Epub 2010 Mar 24.
Deregulated proteolytic activities frequently have causative or exacerbative functions in pathological conditions such as cancer and inflammatory disease. Many proteases therefore represent therapeutic targets, but the generation of successful small molecule drugs is often limited by the ability to achieve sufficient specificity of action. Consequently, several proteases have been deemed as unsuitable drug targets due to the inability to target them successfully. In an effort to circumvent these issues, much interest has recently focused on the development and application of biologic inhibitors. In this review, the latest research in the development of biologic protease inhibitors is examined. This includes a review of engineered kunitz and other inhibitory domains as well as the application of antibodies as therapeutically viable inhibitors.
蛋白水解酶的活性失调通常在癌症和炎症等病理条件下具有因果或加重作用。因此，许多蛋白酶都成为了治疗靶点，但成功开发小分子药物往往受到作用特异性不足的限制。因此，由于无法成功靶向这些蛋白酶，其中一些蛋白酶已被认为不适合作为药物靶点。为了解决这些问题，最近人们对生物抑制剂的开发和应用产生了浓厚的兴趣。在这篇综述中，我们研究了生物蛋白酶抑制剂的最新研究进展。这包括对工程化的 Kunitz 结构域和其他抑制结构域的综述，以及将抗体作为可行的治疗性抑制剂的应用。
