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新型基质金属蛋白酶-9(MMP-9)抑制剂在癌症治疗中的应用。

Novel Matrix Metalloproteinase-9 (MMP-9) Inhibitors in Cancer Treatment.

机构信息

Department of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman 11942, Jordan.

出版信息

Int J Mol Sci. 2023 Jul 28;24(15):12133. doi: 10.3390/ijms241512133.

Abstract

Matrix metalloproteinases (MMPs) belong to a family of zinc-dependent proteolytic metalloenzymes. MMP-9, a member of the gelatinase B family, is characterized as one of the most intricate MMPs. The crucial involvement of MMP-9 in extracellular matrix (ECM) remodeling underscores its significant correlation with each stage of cancer pathogenesis and progression. The design and synthesis of MMP-9 inhibitors is a potentially attractive research area. Unfortunately, to date, there is no effective MMP-9 inhibitor that passes the clinical trials and is approved by the FDA. This review primarily focuses on exploring the diverse strategies employed in the design and advancement of MMP-9 inhibitors, along with their anticancer effects and selectivity. To illuminate the essential structural characteristics necessary for the future design of novel MMP-9 inhibitors, the current narrative review highlights several recently discovered MMP-9 inhibitors exhibiting notable selectivity and potency.

摘要

基质金属蛋白酶(MMPs)属于锌依赖性蛋白水解金属酶家族。MMP-9 是明胶酶 B 家族的成员之一,其特征是最复杂的 MMP 之一。MMP-9 在外基质(ECM)重塑中起着关键作用,这突显了它与癌症发病机制和进展的每个阶段都有密切关系。MMP-9 抑制剂的设计和合成是一个极具吸引力的研究领域。不幸的是,迄今为止,还没有通过临床试验并获得 FDA 批准的有效 MMP-9 抑制剂。本综述主要探讨了设计和开发 MMP-9 抑制剂的多种策略,以及它们的抗癌作用和选择性。为了阐明未来设计新型 MMP-9 抑制剂所需的基本结构特征,本综述重点介绍了几种最近发现的具有显著选择性和效力的 MMP-9 抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7606/10418771/8d04b2af421e/ijms-24-12133-g001.jpg

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