Recent Advances and New Strategies in Targeting Plk1 for Anticancer Therapy.
Recent Advances and New Strategies in Targeting Plk1 for Anticancer Therapy.
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DOI：
10.1016/j.tips.2015.08.013
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发表时间：
2015-12
影响因子：
13.8
通讯作者：
Lee E
中科院分区：
文献类型：
--
作者：
Lee KS;Burke TR Jr;Park JE;Bang JK;Lee E
Polo-like kinase1(Plk1)在调节细胞有丝分裂过程中起关键作用，而有丝分裂过程对细胞增殖至关重要。Plk1的过度表达与人类某些癌症的发生密切相关，大量证据表明Plk1是抗癌治疗开发的一个有吸引力的靶点。靶向Plk1的药物可能针对两个不同的位点：N端催化结构域和C端Polo-box结构域，前者使底物磷酸化，后者对蛋白质-蛋白质相互作用至关重要。在这篇综述中，我们将总结针对这两个领域的Plk1抑制剂开发的最新进展和新的挑战。我们还将讨论设计和开发下一代抑制剂的新策略，以有效治疗Plk1相关的人类疾病。
Polo-like kinase 1 (Plk1) plays key roles in regulating mitotic processes that are critical for cellular proliferation. Overexpression of Plk1 is tightly associated with the development of certain cancers in humans, and a large body of evidence suggests that Plk1 is an attractive target for anticancer therapeutic development. Drugs targeting Plk1 can potentially be directed at two distinct sites: the N-terminal catalytic domain, which phosphorylates substrates, and the C-terminal polo-box domain, which is essential for protein–protein interactions. In this review, we will summarize recent advances and new challenges in the development of Plk1 inhibitors targeting these two domains. We will also discuss novel strategies for designing and developing next-generation inhibitors to effectively treat Plk1-associated human disorders.