Targeting Matrix Metalloproteinases in Cancer: Bringing New Life to Old Ideas.
Targeting Matrix Metalloproteinases in Cancer: Bringing New Life to Old Ideas.
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DOI：
10.1016/j.gendis.2014.12.002
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发表时间：
2015-03-01
期刊：
影响因子：
6.8
通讯作者：
Cao, Jian
中科院分区：
文献类型：
--
作者：
Cathcart, Jillian;Pulkoski-Gross, Ashleigh;Cao, Jian
基质金属蛋白酶(MMPs)是一类锌依赖的内肽酶，是肿瘤进展和患者预后的驱动因子，自从被发现以来，MMPs受到了广泛的研究。尽管早期针对MMPs的计划在临床试验中大多不成功，但根据临床前研究及其在疾病进展中的作用，它们仍然是一个可行的和非常可取的治疗靶点。随着有关这些酶的结构和功能的信息的汇编和生物技术的发展，开发更好的抑制剂的工具是在我们掌握的范围内。高通量筛选和电子药物设计程序的改进方法已经确定了高效、高结合亲和力和表现出良好的药代动力学特征的化合物。最近，药物传递方法或结合在活性部位外的化合物的进展为该领域带来了新的曙光。在这篇综述中，我们重点介绍了MMPs在癌症中的作用，MMPs抑制剂的临床试验，以及针对MMPs在癌症中的靶向的新方法。
Since the identification of matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, as being a driving factor for cancer progression and patient prognosis, MMPs have been studied extensively. Although early programs targeting MMPs were largely unsuccessful in clinical trials, they remain a viable and highly desirable therapeutic target based on preclinical studies and their role in disease progression. As information regarding the structure and function of these proteinases is compiled and biotechnology evolves, tools to develop better inhibitors are within our grasp. Improved methods for high throughput screening and in silico drug design programs have identified compounds which are highly potent, have high binding affinities, and exhibit favorable pharmacokinetic profiles. More recently, advances in drug delivery methods or compounds which bind outside the active site have brought new light to the field. In this review, we highlight the role of MMPs in cancer, clinical trials for MMP inhibitors, and novel approaches to targeting MMPs in cancer.