Selective MMP-13 Inhibitors: Promising Agents for the Therapy of Osteoarthritis

Yichao       Wan; Wei       Li; Zhipeng       Liao; Mi       Yan; Xuwang       Chen; Zilong       Tang
doi:10.2174/0929867326666181217153118
Abstract

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.
Keywords: Osteoarthritis, articular cartilage, MMP-13, zinc-binding group, structure-activity relationship, selective inhibitors.
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DOI https://dx.doi.org/10.2174/0929867326666181217153118	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Selective MMP-13 Inhibitors: Promising Agents for the Therapy of Osteoarthritis

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