Open AccessAdvances with phospholipid signalling as a target for anticancer drug development.
Author(s) -
Garth Powis,
Margareta Berggren,
Alfred Gallegos,
T. Frew,
Simon Hill,
Alan P. Kozikowski,
Rosanne Bonjouklian,
Leon H. Zalkow,
Robert T. Abraham,
Curtis L. Ashendel
Publication year - 1995
Publication title -
acta biochimica polonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.452
H-Index - 78
eISSN - 1734-154X
pISSN - 0001-527X
DOI - 10.18388/abp.1995_4893
Subject(s) - wortmannin , phosphatidylinositol , kinase , cell growth , microbiology and biotechnology , chemistry , cancer cell , signal transduction , inositol , biology , biochemistry , cancer research , cancer , receptor , genetics
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.