Fostriecin and Related Protein Phosphatase Inhibitors
Principal Investigator: Dale Boger
Abstract: A detailed study of fostriecin, a potent and efficacious antitumor agent that inhibits the mitotic entry checkpoint through the selective inhibition of protein phosphatases 2A and 4, and related naturally-occurring and synthetic inhibitors of protein phosphatases (PP) will be conducted. This will include the implementation of an improved second-generation total synthesis of fostriecin, the total synthesis and stereochemical assignment of cytostatin, and the total synthesis and stereochemical assignment of sultriecin. Extensions of the studies to the definition of the fostriecin pharmacophore responsible for its potent and selective PP inhibition and the preparation of more stable and structurally simpler analogues that address issues currently limiting the clinical potential of fostriecin will be pursued.
Funding Period: 2001-12-14 - 2006-11-30
more information: NIH RePORT
- Total synthesis and evaluation of cytostatin, its C10-C11 diastereomers, and additional key analogues: impact on PP2A inhibitionBrian G Lawhorn
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
J Am Chem Soc 128:16720-32. 2006....