The mechanism of selective gene regulation by selective nuclear receptor modulators

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: University of Shizuoka (2020-2021); Toho University (2019)
• Principal Investigator: Kanno Yuichiro 静岡県立大学, 薬学部, 講師 (40453849)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 核内受容体 / 転写因子 / ホルモン / 薬学 / 衛生薬学

Outline of Final Research Achievements

Nuclear receptors are involved in various physiological actions and are involved in various diseases such as endocrine diseases, metabolic diseases, and cancer. Understanding of the regulation mechanism of the physiological function and activity of nuclear receptors is very important for the development of therapeutic agents targeting nuclear receptors. Selective nuclear receptor modulators (SNRM) have been noted as candidate compounds for various therapeutic agents in recent years, but the molecular mechanism of gene-selective expression regulatory mechanism is unknown. In this study, we proved the molecular mechanism based on the model that "selective gene expression regulation by nuclear receptors is determined by the crosstalk of three factors: cofactor, ligand, and target gene / enhancer". As a result, we were able to establish a molecular mechanism based on our model in CAR and androgen receptors.

Free Research Field

衛生薬学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、核内受容体による遺伝子発現機構の基本原理を理解し、選択的核内受容体調節薬の分子基盤を確立することができる。そして、その情報を利用して新たな治療薬候補としての選択的核内受容体調節薬を探索する手法の提案することが可能になる。