Investigation of the mechanism of actions of the helioxanthin-derivative and its application as a multi-kinase inhibitor

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19611
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: Osaka University (2022); Nagasaki University (2021)
• Principal Investigator: Ohba Shinsuke 大阪大学, 大学院歯学研究科, 教授 (20466733)
• Co-Investigator(Kenkyū-buntansha): 森石 武史 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (20380983) ; 松尾 友紀 長崎大学, 医歯薬学総合研究科(歯学系), 技術職員 (40792601) ; 北條 宏徳 東京大学, 大学院医学系研究科(医学部), 准教授 (80788422)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: へリオキサンチン類縁体

Outline of Final Research Achievements

This study aimed to explore the mode of action and target molecules of TH, an osteogenic helioxanthin-derivative, and to assess the possibilities of its application. By taking advantage of genome-wide analysis, bioinformatics, cheminformatics, and molecular biology/biochemistry, we obtained promising candidates for kinases targeted by TH. Furthermore, the data suggest that TH inhibits activities of the candidates, affects regulation of their downstream molecules, and thereby exerts its biological function. In terms of biological functions of TH, we examined whether TH was able to maintain stemness properties of mouse pluripotent stem cells; the data indicated that TH had no obvious effect on the properties.

Free Research Field

発生学・幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

複数のキナーゼがTHの標的分子候補として得られたことはTHがマルチキナーゼ阻害剤であることを示唆しており、骨形成促進剤としてのTHの作用機序の解明につながる。THの作用機序の解明によりその薬理作用を分子レベルで理解することが可能となるだけでなく、副作用の予測が可能となる。その結果、THの骨形成促進作用を利用した骨粗鬆症治療薬、骨修復・骨増生剤としての応用への可能性が広がると期待される。