A small molecule inhibitor of p53-inducible protein phosphatase PPM1D

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.