丝/苏氨酸蛋白激酶Akt及其靶向药物研究进展

Serine/threonine protein kinase Akt and Akt targeting anticancer drug development

丝/苏氨酸蛋白激酶Akt(又名prote in k inase B)在多种人类肿瘤中存在表达或活性失调,并且Akt在调节肿瘤细胞生长、增殖,促进细胞侵袭和转移,促进新生血管生成,以及肿瘤细胞产生化疗、放疗耐受性中起着重要作用,因此,Akt已成为抗肿瘤药物的潜在靶点。以Akt为靶点的药物开发已成为当前研究的热点。目前已开发出多种针对Akt,具有抗肿瘤活性的化合物,如API-2、Akt-I-1、Akt-I-2、DC IEL。这些化合物有可能对Akt异常的肿瘤有高选择性和高疗效,具有良好的应用前景。

Dyregulation of serine/threonine protein kinase Akt/PKB activity is a prominent feature of many human cancers. A large number of studies have demonstrated that Akt plays a key role in mediating cell growth and proliferation, promoting cell migration and invasion, stimulating neoangiogenesis, and protecting from pro-apoptotic stimuli. In view of the highly pleiotropic biologic effects of Akt signaling in multiple aspects of tumor pathophysiology, development of clinically applicable drugs specifically targeting Akt has been the subject of intense research. Up to now, a number of Akt specific inhibitors such as API-2, Akt- I-1, Akt-I-2 and DCIEL have been developed and investigated in pre-clinical studies. These compounds have been shown to potently inhibit growth of tumors with aberrantly expressed or activated Akt, therefore, are likely to be developed as promising targeted anticancer drugs.