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Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation.

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.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Ogasawara S,Kiyota Y,Chuman Y,Kowata A,Yoshimura F,Tanino K,Kamada R,Sakaguchi K

doi

10.1016/j.bmc.2015.08.042

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

6246-9

issue

19

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(15)30024-9

journal_volume

23

pub_type

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