2. Academic Validation
  3. A small molecule inhibitor of p53-inducible protein phosphatase PPM1D

A small molecule inhibitor of p53-inducible protein phosphatase PPM1D

  • Bioorg Med Chem Lett. 2012 Jan 1;22(1):729-32. doi: 10.1016/j.bmcl.2011.10.084.
Hiroaki Yagi 1,  Yoshiro Chuman,  Yuuki Kozakai,  Toshiaki Imagawa,  Yu Takahashi,  Fumihiko Yoshimura,  Keiji Tanino,  Kazuyasu Sakaguchi
Affiliations

Affiliation

  • 1 Laboratory of Biological Chemistry, Department of Chemistry, Faculty of Science, North 10, West 8, Kita-ku, Hokkaido University, Sapporo 060-0810, Japan.
PMID: 22115592 DOI: 10.1016/j.bmcl.2011.10.084
Abstract

PPM1D is a p53-inducible Ser/Thr protein Phosphatase. PPM1D gene amplification and overexpression have been reported in a variety of human tumors, including breast Cancer and neuroblastoma. Because the Phosphatase activity of PPM1D is essential for its oncogenic role, PPM1D inhibitors should be viable anti-cancer agents. In our current study, we showed that SPI-001 was a potent and specific PPM1D inhibitor. SPI-001 inhibited PPM1D Phosphatase activity in PPM1D-overexpressing human breast Cancer cells and increased phosphorylation of p53. Furthermore, SPI-001 suppressed cell proliferation by inducing Apoptosis. Our present study suggested that SPI-001 was a potential lead compound in developing anti-cancer drugs.

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