Advances with phospholipid signalling as a target for anticancer drug development

The phosphatidylinositol-3-kinases (PtdIns-3-kinase) are a family of enzymes involved in the control of cell replication. One member of the family, the mammalian pll0/p85 PtdIns-3-kinase, is a potential target for anticancer drug development because of its role as a component of growth factor and oncogene activated signalling pathways. There are a number of inhibitors of this PtdIns-3-kinase, the most potent being wortmannin (IC50 4 nM). Wortmannin inhibits cancer cell growth and has shown activity against mouse and human tumor xenografts in mice. Other inhibitors of the PtdIns-3-kinase are halogenated quinones which also inhibit cancer cell growth and have some in vivo antitumor activity. Some D-3-deoxy-3-substituted mt/o-inositol analogues and their corresponding Ptdlns analogues have been synthesized. They may act as mi/o-inositol antimetabolites in the PtdIns-3-kinase pathway and they can inhibit cancer cell growth.