Acta Biochim Pol. 1995;42(4):395-403.

Advances with phospholipid signalling as a target for anticancer drug development.

Powis G, Berggren M, Gallegos A, Frew T, Hill S, Kozikowski A, Bonjouklian R, Zalkow L, Abraham R, Ashendel C, et al.

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Arizona Cancer Center, University of Arizona, Tucson 85724, USA.

Abstract

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 p110/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 myo-inositol analogues and their corresponding PtdIns analogues have been synthesized. They may act as myo-inositol antimetabolites in the PtdIns-3-kinase pathway and they can inhibit cancer cell growth.

PMID:: 8852330; [PubMed - indexed for MEDLINE]

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