Submit Manuscript  

Article Details


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

Author(s):

Yichao Wan*, Wei Li, Zhipeng Liao, Mi Yan, Xuwang Chen* and Zilong Tang   Pages 1 - 17 ( 17 )

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:

Osteoarthritis, articular cartilage, MMP-13, zinc-binding group, structure-activity relationship, selective inhibitors

Affiliation:

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, 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, 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, Department of Pharmacy, The Second Hospital of Shandong University, Jinan, Shandong 250033, Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, 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



Read Full-Text article