TAZ activator that promotes cardiomyocytes proliferation by activating YAP/TEAD-mediated transcription, as well as by exerting antioxidant and antiapoptotic activity.
TT-10 (TAZ K) is a TAZ (transcriptional coactivator with PDZ-binding motif) activator that promotes cardiomyocytes (CMs) proliferation (fold-increase by 10 μM TT-10 over untreated control = 5.2/rat CMs/40 hrs & 2.6/human iPSC-derived CMs/48 hrs) by activating YAP (YES-associated protein)/TEAD (transcriptional enhancer factor domain) complex-mediated transcription, as well as by exerting antioxidant and antiapoptotic activity. TT-10 ameliorates myocardial infarction-induced cardiac dysfunction in mice in vivo (10 mg/kg i.p.) at least in part via enhancing clonal expansion of existing cardiomyocytes with nuclear YAP expression.
Journal of molecular and cellular cardiology, 128, 90-95 (2019-01-27)
Since regenerative capacity of adult mammalian myocardium is limited, activation of the endogenous proliferative capacity of existing cardiomyocytes is a potential therapeutic strategy for treating heart diseases accompanied by cardiomyocyte loss. Recently, we performed a compound screening and developed a
JACC. Basic to translational science, 3(5), 639-653 (2018-11-21)
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
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