Screening of phosphorylation dependent 14-3-3 binding inhibitors

2015 Fiscal Year Final Research Report

• Project/Area Number: 24510320
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: WATANABE Nobumoto 国立研究開発法人理化学研究所, 環境資源科学研究センター, ユニットリーダー (90221689)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: タンパク質間相互作用 / 小分子化合物 / １４－３－３タンパク質 / タンパク質リン酸化

Outline of Final Research Achievements

A high-throughput screening (HTS) system was developed and employed to the chemical libraries of the RIKEN NPDepo to identify small molecule compounds with 14-3-3 protein-protein interaction inhibitory activity. We identified small molecule inhibitors of 14-3-3 dependent interaction. While most of these hit compounds inhibited some isoforms of 14-3-3 interaction but not those of other isoforms, one compound was found to inhibit all the 14-3-3 isoform dependent binding. This compound had modest growth inhibitory activity of human cancer cells. To our knowledge, small molecule inhibitor for all the 14-3-3 isoform interaction is not reported yet. Our study demonstrates a potential strategy of inhibiting 14-3-3 interaction in human cancers to induce their growth inhibition using small molecule inhibitors.

Free Research Field

分子細胞生物学