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  • Discovery of a Small Molecule to Increase Cardiomyocytes and Protect the Heart After Ischemic Injury.

Discovery of a Small Molecule to Increase Cardiomyocytes and Protect the Heart After Ischemic Injury.

JACC. Basic to translational science (2018-11-21)
Hironori Hara, Norifumi Takeda, Masaki Kondo, Mio Kubota, Tatsuo Saito, Junichi Maruyama, Takayuki Fujiwara, Sonoko Maemura, Masamichi Ito, Atsuhiko T Naito, Mutsuo Harada, Haruhiro Toko, Seitaro Nomura, Hidetoshi Kumagai, Yuichi Ikeda, Hiroo Ueno, Eiki Takimoto, Hiroshi Akazawa, Hiroyuki Morita, Hiroyuki Aburatani, Yutaka Hata, Masanobu Uchiyama, Issei Komuro
ABSTRACT

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 YES-associated protein and transcriptional enhancer factor domain activities in cardiomyocytes. We synthesized a novel fluorine-containing TT-10 (C11H10FN3OS2) from the biologically hit compound. TT-10 promoted cardiomyocyte proliferation and simultaneously exerted antioxidant and antiapoptotic effects in vitro. TT-10 treatment in mice ameliorated myocardial infarction-induced cardiac dysfunction at least in part via enhancing clonal expansion of existing cardiomyocytes with nuclear YES-associated protein expression. Stimulating cardiomyocyte proliferation and/or protection with TT-10 might complement current therapies for myocardial infarction.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
TT-10, ≥98% (HPLC)