The Wild-type p53-Induced Phosphatase (Wip1, PPM1D) is an oncogenic type 2C serine/threonine phosphatase that negatively regulates key regulatory proteins in the DNA damage response pathway.  Amplification of the PPM1D gene locus on 17q23 has also been reported in various cancers and Wip1 overexpression is believed to promote tumorigenesis by inactivating the tumor suppressor function of multiple substrates.  These attributes provide evidence for the therapeutic potential of inhibiting Wip1 as a strategy to treat certain cancers.  Here we report the discovery of a series of selective allosteric small molecule inhibitors of Wip1 phosphatase.  The detailed characterization of the mechanism of action and key structure-activity relationships for this series will be presented.

Allosteric inhibition of the oncogenic serine/threonine phosphatase Wip1

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.