Drug discovery targeting Hippo-YAP pathway for heart regeneration
| Project/Area Number |
17K15987
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HARA Hironori 東京大学, 医学部附属病院, 助教 (60792439)
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| Research Collaborator |
Takeda Norifumi
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 心筋再生 / Hippo経路 / YAP |
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| Outline of Final Research Achievements |
Accumulating data suggest that new cardiomyocytes in adults are generated from existing cardiomyocytes throughout life. To enhance the endogenous cardiac regeneration, we performed chemical screenings to identify compounds that activate pro-proliferative YAP and TEAD activities in cardiomyocytes. We synthesized a novel fluorine-containing compound (TT-10) from the biologically hit compound. TT-10 treatment in mice ameliorated myocardial infarction-induced cardiac dysfunction. In addition, TT-10 markedly promoted cell cycle activation and increased cell division of human induced pluripotent stem cell-derived cardiomyocytes. Stimulating cardiomyocyte proliferation and/or protection with TT-10 might complement current therapies for myocardial infarction.
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| Academic Significance and Societal Importance of the Research Achievements |
社会の高齢化に伴い、虚血性心疾患・慢性心不全を患う患者数が増加している。既存の虚血性心疾患・慢性心不全に対する治療に、本研究のような「内因性の心筋再生の増幅」を用いた治療を併用することで、これまで以上の治療効果を期待できる。また、化合物による治療は、患者への侵襲・安全性や費用対効果などの点からも有効といえる。本研究の成果は、心疾患による死亡を減らし得るため社会に与える貢献も極めて大きいと考えられる。
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] Discovery of a Small Molecule to Increase Cardiomyocytes and Protect the Heart After Ischemic Injury2018
Author(s)
Hara H, Takeda N, Kondo M, Kubota M, Saito T, Maruyama J, Fujiwara T, Maemura S, Ito M, Naito AT, Harada M, Toko H, Nomura S, Kumagai H, Ikeda Y, Ueno H, Takimoto E, Akazawa H, Morita H, Aburatani H, Hata Y, Uchiyama M, Komuro I.
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Journal Title
JACC: Basic to Translational Science
Volume: 3
Issue: 5
Pages: 639-653
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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