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 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.
Powis
G
G
Arizona Cancer Center, University of Arizona, Tucson 85724, USA.
Berggren
M
M
Gallegos
A
A
Frew
T
T
Hill
S
S
Kozikowski
A
A
Bonjouklian
R
R
Zalkow
L
L
Abraham
R
R
Ashendel
C
C
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017261:Glycosylphosphatidylinositols / Q000037:antagonists & inhibitors; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology; D009285:Naphthoquinones / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases; D010743:Phospholipids / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D000077191:Wortmannin
D000730:Androstadienes; D000970:Antineoplastic Agents; D017261:Glycosylphosphatidylinositols; D009285:Naphthoquinones; D010743:Phospholipids; D007294:Inositol; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000077191:Wortmannin