title: A small molecule inhibitor of p53-inducible protein phosphatase PPM1D.
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.
authors: Laboratory of Biological Chemistry, Department of Chemistry, Faculty of Science, North 10, West 8, Kita-ku, Hokkaido University, Sapporo 060-0810, Japan.
authors: Hiroaki
authors: H
authors: Yagi
authors: Yoshiro
authors: Y
authors: Chuman
authors: Yuuki
authors: Y
authors: Kozakai
authors: Toshiaki
authors: T
authors: Imagawa
authors: Yu
authors: Y
authors: Takahashi
authors: Fumihiko
authors: F
authors: Yoshimura
authors: Keiji
authors: K
authors: Tanino
authors: Kazuyasu
authors: K
authors: Sakaguchi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy*; D010616:Phenanthrenes / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry; D010766:Phosphorylation; D000071636:Protein Phosphatase 2C; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007211:Indoles; D010616:Phenanthrenes; C573895:SPI-001; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C007293:DAPI; C085377:MATK protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C000607458:PPM1D protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C; D010744:Phosphoric Monoester Hydrolases