Development of novel selective androgen receptor modulators for the treatment of skeletal and muscle diseases.
| Project/Area Number |
17K08266
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo University of Agriculture and Technology |
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Principal Investigator |
HIRATA MICHIKO 東京農工大学, 工学(系)研究科(研究院), 講師 (40544060)
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| 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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 骨粗鬆症 / サルコペニア |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(66 results)
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[Journal Article] Beta-cryptoxanthin inhibits lipopolysaccharide-induced osteoclast differentiation and bone resorption via the suppression of inhibitor of NF-κB kinase activity.2019
Author(s)
Hirata N , Ichimaru R , Tominari T , Matsumoto C, Watanabe K ,Taniguchi K , Hirata M , Ma S, Suzuki K , Grundler FM , Miyaura C, Inada M
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Journal Title
Nutrients
Volume: 11
Issue: 2
Pages: 368-368
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Hypergravity and microgravity exhibited reversal effects on the bone and muscle mass in mice.2019
Author(s)
Tominari T, Ichimaru R, Taniguchi K, Yumoto A, Shirakawa M, Matsumoto C, Watanabe K, Hirata M, Itoh Y, Shiba D, Miyaura C, Inada M
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Journal Title
Sci Rep.
Volume: 9(1)
Pages: 6614-6614
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Structure-activity relationship of anthocyanidins as an inhibitory effect on osteoclast differentiation.2018
Author(s)
Hirata N, Tominari T, Ichimaru R, Taniguchi K, Matsumoto C, Watanabe K, Hirata M, Ma S, Suzuki K, Grundler FM, Miyaura C, Inada M
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Journal Title
BPB_Reports
Volume: 2
Pages: 1-6
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Raloxifene reduces the risk of local alveolar bone destruction in a mouse model of periodontitis combined with systemic postmenopausal osteoporosis.2018
Author(s)
Ichimaru R, Tominari T, Yoshinouchi S, Matsumoto C, Watanabe K, Hirata M, Numabe Y, Murphy G, Nagase H, Miyaura C, Inada M
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Journal Title
Arch. Oral Biol
Volume: 85
Pages: 98-103
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Raloxifene reduces the risk of local alveolar bone destruction in a mouse model of periodontitis combined with systemic postmenopausal osteoporosis.2018
Author(s)
Ichimaru R, Tominari T, Yoshinouchi S, Matsumoto C, Watanabe K, Hirata M, Numabe Y, Murphy G, Nagase H, Miyaura C, Inada M
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Journal Title
Arch. Oral Biol.
Volume: 85
Pages: 98-103
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Indoxyl sulfate, a uremic toxin in chronic kidney disease, suppresses both bone formation and bone resorption.2017
Author(s)
Watanabe K, Tominari T, Hirata M, Matsumoto C, Hirata J, Murphy G, Nagase H, Miyaura C, Inada M
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Journal Title
FEBS Open Bio.
Volume: 7
Pages: 1178-1185
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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