Akt抑制剂的研究进展

Akt是一类丝/苏氨酸蛋白激酶，是磷脂酰肌醇-3激酶(PI3K)的下游靶点，通过磷酸化其下游一系列底物来促进细胞生长、代谢、凋亡、血管新生等重要的细胞生物学过程，其在多种恶性肿瘤中都存在过度表达或活性失调的现象。研究表明，通过抑制Akt的活性能有效地遏制肿瘤的生长，因此研发新型的Akt抑制剂已经成为抗肿瘤药物开发的热点之一。Akt抑制剂主要分为PH结构域抑制剂、ATP竞争性抑制剂、变构抑制剂等，目前已有多个Akt的抑制剂进入临床研究。本文综述了不同类型的Akt抑制剂的Akt抑制活性及特点，为开发新型抗肿瘤药物提供参考。

Research Progress for Akt Inhibitors

Akt (PKB), a kind of serine/threonine protein kinase, is the downstream target of phosphatidyl inositol-3 kinase (PI3K), and it can promote cell growth, metabolism, apoptosis, angiogenesis, and other important process of cell biology by affecting phosphorylation of its downstream substrates. There exists the phenomenon of Akt overexpression or activity disorder in a variety of human malignant tumor. Research shows that it can effectively inhibit tumor cell proliferation by inhibiting the activity of Akt. Design and development of novel Akt inhibitors has been one of the hot spot of antitumor drug research. Akt inhibitor consists of PH structure domain inhibitors, ATP competitive inhibitors, allosteric inhibitors, etc., and currently, several small molecule Akt inhibitors have been into clinical stage. This paper reviews Akt inhibitory activity and feature of different Akt inhibitors for guiding the development of novel antitumor drugs.