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Recent Research Advances in Selective Matrix Metalloproteinase‐13 Inhibitors as Anti‐Osteoarthritis Agents
Author(s) -
Xie XinWen,
Wan RenZhong,
Liu ZhaoPeng
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700349
Subject(s) - hydroxamic acid , chemistry , matrix metalloproteinase , pyrazole , enzyme , matrix metalloproteinase inhibitor , hydantoin , biochemistry , stereochemistry , binding site , combinatorial chemistry , pharmacology , biology
Matrix metalloproteinase‐13 (MMP‐13) plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). The subtle differences between the S1′ loop of MMP‐13 and that of other MMPs offer a structural base for the design of selective MMP‐13 inhibitors to mitigate the unperceived risk associated with inhibiting other MMP isoforms. In this review, we summarize zinc‐binding and non‐zinc‐binding selective MMP‐13 inhibitors. The zinc‐binding MMP‐13 inhibitors contain a small set of zinc‐binding groups (ZBGs), including hydroxamic acid, pyrimidinetrione, reversed hydroxamic acid and hydantoin, carboxylic acid, 1,2,4,‐triazole, and 1,2,4,‐triazolone. The non‐zinc‐binding MMP‐13 inhibitors have different structural scaffolds, including diphenyl ethers, biaryls (aryltetrazoliums, arylfurans, pyrazole‐indoles), pyrimidines, and aryl/cycloalkyl‐fused pyrimidines. This review provides a systematic overview of recent developments in MMP‐13 inhibitors for the treatment of OA, with emphasis on their enzyme inhibitory potency, selectivity, and biological activities, and highlights the various binding modes of typical inhibitors with MMP‐13.