ヒト多能性幹細胞からの効率的な心筋細胞分化に向けた新規低分子化合物の開発

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Author: 岸野, 喜一

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Publication date: 2019

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Note (General)：: type:text心筋分化誘導において分化初期のBMPシグナルの活性化が重要であり、同シグナルを活性化する低分子化合物候補の探索を行った。RNAiとルシフェラーゼアッセイにより選出した標的因子に結合可能な化合物のin silico探索を行い、最終的に結合親和性の高い50化合物を選出した。候補化合物を...

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科研費研究者番号 : 20594568

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Material Type: 文書・図像類
Title: ヒト多能性幹細胞からの効率的な心筋細胞分化に向けた新規低分子化合物の開発
Author/Editor: 岸野, 喜一
Author Heading: 岸野, 喜一
Publication Date: 2019
Publication Date (W3CDTF): 2019
Alternative Title: ヒトタノウセイカンサイボウカラノコウリツテキナシンキンサイボウブンカニムケタシンキテイブンシカゴウブツノカイハツ
Hito tanōsei kansaibō kara no kōritsutekina shinkin saibō bunka ni muketa shinki teibunshi kagōbutsu no kaihatsu
Novel small molecule chemical compounds for promoting the differentiation efficiency of iPS-derived cardiomyocytes
Periodical title: 科学研究費補助金研究成果報告書
Text Language Code: jpn
eng
Subject Heading: 再生医療,ヒトiPS細胞由来心筋細胞,BMPシグナル
Target Audience: 一般
Note (General): type:text
心筋分化誘導において分化初期のBMPシグナルの活性化が重要であり、同シグナルを活性化する低分子化合物候補の探索を行った。RNAiとルシフェラーゼアッセイにより選出した標的因子に結合可能な化合物のin silico探索を行い、最終的に結合親和性の高い50化合物を選出した。候補化合物をヒトiPS細胞の心筋分化誘導系に添加し、分化誘導促進効果をFACS、PCR、免疫染色を用いて定量的に評価した。結果、化合物の有効濃度が高い為、細胞毒性を認めてはいるが、低濃度において、心筋分化効率の改善を示唆する結果が確認された。より低濃度で有効性を認める化合物の二次探索を行っている。 In cardiac differentiation, activation of BMP signaling in the early stage is important. We searched for small molecule compound activating BMP signaling. To develop the screening system, we used luciferase assay including BMP-responsive element and RNA interference. Among many candidate regulators, we found that knockdown of target factor significantly enhanced luciferase activity. Next, to identify novel antagonists which have high binding-affinity for the candidate factor, we screened compounds by in silico protein structure analysis and narrowed down to 50 candidates among chemical compound data libraries. Next, to test the efficacy of candidate compounds, we confirmed that compounds promoted cardiac differentiation in human iPS cells. Finally, calculating the correlation function between the chemical structure and the enhancement of BMP signaling activity, we have planned to perform full-screening to identify high efficient lead compounds among massive compound data libraries.
研究種目 : 若手研究研究期間 : 2018～2019 課題番号 : 18K15902 研究分野 : 循環器、心筋再生
Access Restrictions: 限定公開
Related Material: 科研費研究者番号 : 20594568
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 慶應義塾大学 : 慶應義塾大学学術情報リポジトリ