Key Laboratory of Theoretical Organic Chemistry and Functional Molecule, Ministry of Education, Hunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China.
Hunan Provincial College Key Laboratory of QSAR/QSPR, Hunan Provincial Key Lab of Advanced Materials for New Energy Storage and conversion, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China.
Curr Med Chem. 2020;27(22):3753-3769. doi: 10.2174/0929867326666181217153118.
Osteoarthritis (OA) is an age-related degenerative disease, which is characterized by chronic joint pain, inflammation and the damage of joint cartilage. At present, steroidal drugs and nonsteroidal anti-inflammatory drugs (NSAIDS), selective cyclooxygenase-2 (COX-2) inhibitors, are the first-line drugs for the treatment of OA. However, these drugs could lead to some cardiovascular side effects. Therefore, it is urgent to develop novel agents for the treatment of OA. Matrix metalloproteinase-13 (MMP-13), an important member of matrix metalloproteinases (MMPs) family, plays a vital role by degrading type II collagen in articular cartilage and bone in OA. It is noted that MMP-13 is specially expressed in the OA patients, and not in normal adults. In addition, broadspectrum MMP inhibitors could result in some painful and joint-stiffening side effects, called musculoskeletal syndrome (MSS) in the clinical trials. Thus, developing selective MMP-13 inhibitors is a potential strategy for the therapy of OA. In this review, we summarize the recent progress of selective MMP-13 inhibitors including two subfamilies, namely zinc-binding and non-zinc-binding selective MMP-13 inhibitors.
骨关节炎（OA）是一种与年龄相关的退行性疾病，其特征为慢性关节疼痛、炎症和关节软骨损伤。目前，甾体药物和非甾体抗炎药（NSAIDs）、选择性环氧化酶-2（COX-2）抑制剂是治疗 OA 的一线药物。然而，这些药物可能导致一些心血管副作用。因此，迫切需要开发治疗 OA 的新型药物。基质金属蛋白酶-13（MMP-13）是基质金属蛋白酶（MMPs）家族的重要成员，通过降解关节软骨和骨中的 II 型胶原在 OA 中发挥重要作用。值得注意的是，MMP-13 仅在 OA 患者中特异性表达，而在正常成年人中不表达。此外，广谱 MMP 抑制剂可能会导致一些疼痛和关节僵硬的副作用，在临床试验中称为肌肉骨骼综合征（MSS）。因此，开发选择性 MMP-13 抑制剂是治疗 OA 的一种潜在策略。本综述总结了包括锌结合和非锌结合选择性 MMP-13 抑制剂在内的两类选择性 MMP-13 抑制剂的最新进展。
