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. 2018 Dec 17.
doi: 10.2174/0929867326666181217153118. Online ahead of print.

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

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

Yichao Wan et al. Curr Med Chem. .

Abstract

Osteoarthritis (OA) is an age-related degenerative disease, which is characterized by the 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, not in the normal adults. In addition, broad-spectrum 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: MMP-13; Osteoarthritis; articular cartilage; selective inhibitors; structure-activity relationship; zinc-binding group.

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