Discovery of novel selenium derivatives as Pin1 inhibitors by high-throughput screening
- Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198 (Japan)
- Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Kanagawa, 236-0004 (Japan)
- Bio-Active Compounds Discovery Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, 351-0198 (Japan)
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. -- Highlights: •Novel screening for Pin1 inhibitors based on Pin1 binding is developed. •A novel selenium compound is discovered as Pin1 inhibitor. •Activity guided chemical synthesis of selenium derivatives resulted potent Pin1 inhibitors.
- OSTI ID:
- 22598756
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 474, Issue 3; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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