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	Hiroaki Yagi, Yoshiro Chuman, Yuuki Kozakai, Toshiaki Imagawa, Yu Takahashi, Fumihiko Yoshimura, Keiji Tanino, Kazuyasu Sakaguchi
Journal	Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 1 Pg. 729-32 (Jan 01 2012) ISSN: 1464-3405 [Electronic] England
PMID	22115592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References	Antineoplastic Agents Cell Cycle Proteins DNA-Binding Proteins Indoles Phenanthrenes SPI-001 Tumor Suppressor Protein p53 Tumor Suppressor Proteins DAPI MATK protein, human Proto-Oncogene Proteins pp60(c-src) ATM protein, human Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases PPM1D protein, human Phosphoprotein Phosphatases Protein Phosphatase 2C Phosphoric Monoester Hydrolases
Topics	Antineoplastic Agents (pharmacology) Apoptosis Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins (metabolism) Cell Line, Tumor Cell Proliferation DNA-Binding Proteins (metabolism) Dose-Response Relationship, Drug Humans Indoles (pharmacology) Inhibitory Concentration 50 Models, Chemical Neoplasms (drug therapy) Phenanthrenes (pharmacology) Phosphoprotein Phosphatases (antagonists & inhibitors) Phosphoric Monoester Hydrolases (chemistry) Phosphorylation Protein Phosphatase 2C Protein Serine-Threonine Kinases (metabolism) Proto-Oncogene Proteins pp60(c-src) (metabolism) Time Factors Tumor Suppressor Protein p53 (metabolism) Tumor Suppressor Proteins (metabolism)

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