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KAKEN_24310167seika.pdf
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Title |
Title |
Pirin阻害剤による骨疾患薬の開発
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Kana |
Pirin ソガイザイ ニ ヨル コツシッカンヤク ノ カイハツ
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Pirin sogaizai ni yoru kotsushikkanyaku no kaihatsu
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Development of novel drug for bone-related diseases using Pirin inhibitors
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清水, 史郎
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シミズ, シロウ
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Simizu, Siro
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慶應義塾大学・理工学部・准教授
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Research team head
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科研費研究者番号 : 30312268
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梅澤, 一夫
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ウメザワ, カズオ
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Umezawa, Kazuo
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愛知医科大学・医学部・教授
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Research team member
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科研費研究者番号 : 70114402
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2015
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科学研究費補助金研究成果報告書
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2014
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Abstract |
骨関連疾患数はわが国でも増加しており, ビスホスホネート製剤などの薬剤が使用されているが, これらの薬剤は副作用も報告されている。新規の骨疾患治療薬としてPirin阻害剤のTPh Aに着目し実験を行った結果, 細胞毒性が発揮されない濃度において複数のTPh A誘導体がPirin阻害とは独立してRANKLにより誘導される破骨細胞の分化を阻害した。これら化合物は, RANKLによるMAPKsのリン酸化などは阻害せずに, c-FosやDC-STAMPの発現を抑制したことから, 新しい機構で作用する薬剤のシードの可能性が考えられる。
The number of bone-related disease patients is increasing in Japan. At present, bisphosphonates are widely used for these diseases, but their severe side effects are impossible to ignore.
We focused on TPh A, a Pirin inhibitor, as a novel drug for such diseases. We assayed many derivatives of TPh A and found that 2 compounds inhibited RANKL-induced osteoclastgenesis on Pirin-independent manner without cytotoxicity. These compounds did not suppress phosphorylation of MAPKs, although its inhibited expression of c-Fos and DC-STAMP. Therefore, it is suggested that the compounds we found might be candidates for drugs of bone-related diseases.
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研究種目 : 基盤研究(B)
研究期間 : 2012~2014
課題番号 : 24310167
研究分野 : ケミカルバイオロジー
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Aug 5, 2019 | | 著者,著者版フラグ を変更 |
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