The development of phosphatidylinositol ether lipid analogues as inhibitors of the serine/threonine kinase, Akt

被引：56

作者：

Gills, JJ ^{[1
]}

Dennis, PA ^{[1
]}

机构：

[1] NCI, Canc Therapeut Branch, Ctr Canc Res, Navy Med Oncol, Bethesda, MD 20889 USA

来源：

EXPERT OPINION ON INVESTIGATIONAL DRUGS | 2004年 / 13卷 / 07期

关键词：

Akt; cancer; phosphatidylinositol ether lipid analogue; pleckstrin homology domain;

D O I：

10.1517/13543784.13.7.787

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The serine/threonine kinase Akt is a component of the phosphatidylinositol 3'-kinase/Akt signal transduction pathway that is activated by receptor tyrosine kinases, -activated Ras and integrins. As Akt regulates many processes crucial to carcinogenesis, and Akt activation has been observed in human cancers, intense efforts are underway to develop Akt inhibitors as cancer therapeutics. Towards this aim, phosphatidylinositol ether lipid analogues (PlAs), which are structurally similar to the products of phosphatidylinositol 3'-kinase, have been synthesised. PlAs inhibit Akt translocation, phosphorylation and kinase activity. Furthermore, they selectively induce apoptosis in cancer cell lines that depend on Akt for survival. This review will trace the development of PlAs, cover the biological activities of PlAs and discuss future steps and challenges in their development.

引用

页码：787 / 797

页数：11

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