金属基质蛋白酶类抗癌靶点及靶向多肽药物研究进展

Research progress of matrix metalloproteinase-related anticancer targets and peptide drugs

金属基质蛋白酶(MMP)作为锌依赖性肽链内切酶,家族成员繁多,与肿瘤的发生发展密切相关,所以经常将MMP作为抗癌靶点进行药物研究。早期的MMP靶点类抗癌药物是MMP的天然抑制蛋白——MMP组织抑制剂(TIMP),后来通过研究又发现了很多化学分子抑制剂(如马马司他、坦诺司他、普啉司他),但这些化学药物临床有效性和安全性较差,很难应用于临床。多肽类抑制剂由于具有相对分子质量小、结合效率高等优点比较适合作为金属基质蛋白酶的分子抑制剂或靶向释药载体。本文对MMP这一靶点和抗癌药物的研究进展进行介绍。

The matrix metalloproteinase （MMP） as zinc-dependent endopeptidase enzymes has many members in this family, and MMPs are closely related to tumor development. At the early stage of research, anticancer drugs targeting MMP is natural tissue inhibitors of MMP （TIMP）. Then, through the study about the MMP targets, many chemical molecule inhibitors （such as marimastat, tanomastat and prinomastat） were also found, but chemical drugs are difficult to be used in clinical due to their poor efficacy and low safety. Because of small molecular weight and high affinity with targets, peptides are more appropriate to be molecular inhibitors or drug delivery carriers. The research progress of MMP-related targets and anticancer drugs was introduced in this paper.