Development of novel selective androgen receptor modulators for the treatment of skeletal and muscle diseases.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: HIRATA MICHIKO 東京農工大学, 工学(系)研究科(研究院), 講師 (40544060)
• Co-Investigator(Kenkyū-buntansha): 宮浦 千里 東京農工大学, 工学(系)研究科(研究院), 教授 (20138382)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 骨粗鬆症 / サルコペニア

Outline of Final Research Achievements

Loss of musculoskeletal mass and function is a natural ageing trait, and osteoporosis and sarcopenia are increasing in older people, but androgen therapy is not generally used due to the perceived side effects, such as prostate cancer. Therefore novel selective androgen receptor modulators (SARMs) are potential candidate anabolic compounds that maintain bone mass and muscle function. In this study, we have demonstrated that BA321, a novel carborane compound, bound to not only AR, but also ERs with a high binding affinity, and completely restored the bone loss in ORX mice. Since BA321 did not influence the muscle and sex organ in the males, it is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male.

Free Research Field

生物系薬

Academic Significance and Societal Importance of the Research Achievements

本研究により、新規カルボラン化合物BA321は、骨量低下・筋量低下モデル動物の大腿骨骨密度を回復させる効果を有するが、筋量ならびに男性生殖器への作用を示さないことを明確に示した。従って、BA321は骨組織選択的に作用するSARMである可能性を示唆し、超高齢社会の到来により、老人性骨粗鬆症の罹患者が増加している現在において、新規な骨粗鬆症の治療薬の候補となり得る。また、質量分析イメージングを用い、骨と筋での動態観察の基盤を確立できたことは、今後のドラッグデリバリー解析において、有用な解析方法として応用が期待される。