Targeting transcription and epigenetic factors through modulation of protein-protein interactions

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03685
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Goyama Susumu 東京大学, 大学院新領域創成科学研究科, 教授 (80431849)
• Co-Investigator(Kenkyū-buntansha): 長門石 曉 東京大学, 医科学研究所, 特任准教授 (30550248) ; 高橋 宏隆 愛媛大学, プロテオサイエンスセンター, 准教授 (70432804)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 骨髄系腫瘍 / 転写因子 / エピゲノム制御因子 / タンパク質間相互作用

Outline of Final Research Achievements

The development of drugs targeting transcription and epigenomic factors has been considered difficult, but recent technological innovations have enabled drug discovery based on Protein-Protein Interaction (PPI) regulation. In this study, we utilized the latest PPI regulation technology to identify compounds that inhibit transcription factor RUNX1-CBFB binding, compounds that bind to RUNX1 and E3 ubiquitin ligase STUB1, and compounds that inhibit epigenomic regulator ASXL1-BAP1 binding. In addition, RUNX1-targeted nucleic acid drugs were developed. Based on these results, the development of novel drugs targeting hematopoietic transcription factors and epigenetic regulators will be promoted in the future.

Free Research Field

血液腫瘍学

Academic Significance and Societal Importance of the Research Achievements

転写因子やエピゲノム制御因子は、様々な遺伝子の発現を制御する役割を持ち、がんの発症・進展にも深く関与しています。しかし、転写・エピゲノム因子を標的とする薬剤の開発は難しいと考えられてきました。本研究では、タンパク質間の相互作用を制御する最新の技術を活用して、これまで有効な治療薬が存在しなかった転写因子RUNX1や、エピゲノム制御因子ASXL1の機能を阻害する薬剤を開発しました。