2. Academic Validation
  3. Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation

Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation

  • Bioorg Med Chem. 2015 Oct 1;23(19):6246-9. doi: 10.1016/j.bmc.2015.08.042.
Sari Ogasawara 1,  Yuhei Kiyota 1,  Yoshiro Chuman 1,  Ayano Kowata 2,  Fumihiko Yoshimura 2,  Keiji Tanino 2,  Rui Kamada 1,  Kazuyasu Sakaguchi 3
Affiliations

Affiliations

  • 1 Laboratory of Biological Chemistry, Department of Chemistry, Faculty of Science, Hokkaido University, North 10, West 8, Kita-ku, Sapporo 060-0810, Japan.
  • 2 Laboratory of Organic Chemistry II, Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan.
  • 3 Laboratory of Biological Chemistry, Department of Chemistry, Faculty of Science, Hokkaido University, North 10, West 8, Kita-ku, Sapporo 060-0810, Japan. Electronic address: kazuyasu@sci.hokudai.ac.jp.
PMID: 26358280 DOI: 10.1016/j.bmc.2015.08.042
Abstract

Protein Phosphatase magnesium-dependent 1δ (PPM1D, Wip1) is a p53 inducible serine/threonine Phosphatase. PPM1D is a promising target protein in Cancer therapy since overexpression, missense mutations, truncating mutations, and gene amplification of PPM1D are reported in many tumors, including breast Cancer and neuroblastoma. Herein, we report that a specific inhibitor, SL-176 that can be readily synthesized in 10 steps, significantly inhibits proliferation of a breast Cancer cell line overexpressing PPM1D and induces G2/M arrest and Apoptosis. SL-176 decreases PPM1D Enzyme activity potently and specifically in vitro. These results demonstrate that SL-176 could be a useful lead compound in the development of effective anti-cancer agents.

Keywords

Anti-tumor; Apoptosis; Dephosphorylation; Inhibitors; Protein phosphatase.

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