High throughput screening to identify small molecules inducing receptor internalization as potential aniticancer agents

2015 Fiscal Year Final Research Report

• Project/Area Number: 26560441
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: The University of Tokyo
• Principal Investigator: Asanuma Daisuke 東京大学, 医学(系)研究科(研究院), 助教 (10611204)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ハイスループットスクリーニングシステム / 受容体 / ダウンレギュレーション

Outline of Final Research Achievements

Enhanced expression of receptor tyrosine kinases in cancers, e.g., human epidermal growth factor receptor 2 (HER2) in ovarian and breast cancers, is associated with aggressiveness. Blockade of receptor signaling via induction of receptor internalization and degradation is a promising approach for cancer therapy. By employing a recently developed acidic-pH-activatable probe (Asanuma, D. et al., Angew. Chem. Int. Ed. Engl. 53, 6085-6089 (2014)), a cell-based high-throughput screening system was developed to identify molecules that induce HER2 internalization. From a ~155,000 small-molecule library, three hit compounds that induce internalization and degradation of HER2 were successfully identified.

Free Research Field

ケミカルバイオロジー