2. Academic Validation
  3. Discovery of novel selenium derivatives as Pin1 inhibitors by high-throughput screening

Discovery of novel selenium derivatives as Pin1 inhibitors by high-throughput screening

  • Biochem Biophys Res Commun. 2016 Jun 3;474(3):528-533. doi: 10.1016/j.bbrc.2016.04.124.
Amit Subedi 1,  Takeshi Shimizu 2,  Akihide Ryo 3,  Emiko Sanada 4,  Nobumoto Watanabe 5,  Hiroyuki Osada 6
Affiliations

Affiliations

  • 1 Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198, Japan; Graduate School of Science and Engineering, Saitama University, Saitama, 338-8570, Japan.
  • 2 Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198, Japan.
  • 3 Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Kanagawa, 236-0004, Japan.
  • 4 Bio-Active Compounds Discovery Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198, Japan.
  • 5 Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198, Japan; Bio-Active Compounds Discovery Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198, Japan.
  • 6 Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198, Japan; Graduate School of Science and Engineering, Saitama University, Saitama, 338-8570, Japan. Electronic address: [email protected].
PMID: 27120460 DOI: 10.1016/j.bbrc.2016.04.124
Abstract

Peptidyl prolyl cis/trans isomerization by PIN1 regulates various oncogenic signals during Cancer progression, and its inhibition through multiple approaches has established PIN1 as a therapeutic target. However, lack of simplified screening systems has limited the discovery of potent PIN1 inhibitors. We utilized phosphorylation-dependent binding of PIN1 to its specific substrate to develop a screening system for PIN1 inhibitors. Using this system, we screened a chemical library, and identified a novel selenium derivative as PIN1 Inhibitor. Based on structure-activity guided chemical synthesis, we developed more potent PIN1 inhibitors that inhibited Cancer cell proliferation.

Keywords

Cancer; High-throughput screening; PPIase; Pin1; Selenium.

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