Matrix metalloproteinases (MMPs) are a large family of enzymes that degrade the extracellular matrix (ECM). Under pathologic conditions, overexpression of MMPs or insufficient control by tissue inhibitors of MMPs (TIMPs) results in the dysregulation of tissue remodeling and causes a variety of diseases such as encephalomyelitis, rheumatoid arthritis, Alzheimer's disease and tumors. Therefore, the high affinity of MMPs for biomolecules renders them attractive targets for inhibition when homeostasis breaks down in the ECM. There are 4 generations of MMP inhibitors (MMPIs), ranging from small molecules or peptides to antibodies and protein-engineered inhibitors of metalloproteinase. Although a plethora of MMPIs has been synthesized, most of them have failed in clinical trials or are still in the laboratory stage of development. The present review summarizes the development of MMPIs, their associated problems and discusses future directions for the development of the future generations of MMPIs.

中文翻译：

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基质金属蛋白酶抑制剂的过去，现在和将来的观点。

基质金属蛋白酶（MMP）是降解细胞外基质（ECM）的一大类酶。在病理条件下，MMPs的过度表达或MMPs组织抑制剂（TIMPs）的控制不足会导致组织重塑失调，并引起多种疾病，例如脑脊髓炎，类风湿性关节炎，阿尔茨海默氏病和肿瘤。因此，当ECM中的稳态失衡时，MMP对生物分子的高亲和力使其成为有吸引力的抑制靶标。MMP抑制剂（MMPI）共有4代，从小分子或肽到金属蛋白酶的抗体和蛋白质工程抑制剂。尽管已经合成了许多MMPI，但大多数MMPI在临床试验中失败或仍处于实验室开发阶段。