エピジェネティクスを標的とする創薬・ケミカルバイオロジー研究

抄録

Histone modifications such as lysine methylation control gene transcription independently on DNA base sequence. Such modification system, which is called "epigenetics," plays important roles in regulating cellular functions including cell cycle, immunoresponses, and signal transduction. However, epigenetic aberrations have been found in many abnormal cells and are associated with various diseases such as cancer and neurodegenerative disorders. Therefore, controlling epigenetics by small molecules has been of interest both in chemical biology and in epigenetic therapy. To establish such technology, we have studied epigenetic inhibitors focusing on histone modification enzymes, especially on histone lysine demethylases (KDMs).  

Lysine-specific demethylase 1 (LSD1) is associated with several disease states, such as cancer. Therefore, LSD1-selective inhibitors have the potential to become therapeutic agents such as anticancer agents. Lysine demethylase 5C (KDM5C) has been proposed as an oncogene in prostate cancer cells and is also associated with Huntington's disease. Therefore, KDM5C inhibitors are of interest as biological tools for studying the functions of KDM5C, as well as candidate therapeutic agents for cancers and neurological disorders. Recently, we have identified an LSD1-selective inhibitor and a KDM5C-selective inhibitor. In this meeting, the details of the inhibitors will be presented.