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Updated: May 27, 2026

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
Published on: April 29, 2022
A small molecule inhibitor of p53-inducible protein phosphatase PPM1D
Hiroaki Yagi1, Yoshiro Chuman, Yuuki Kozakai
1Laboratory of Biological Chemistry, Department of Chemistry, Faculty of Science, North 10, West 8, Kita-ku, Hokkaido University, Sapporo 060-0810, Japan.
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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