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In doxorubicin (Dox)-treated mice, MNF reduced mortality and body weight loss, while improving cardiac function and cardiomyocyte viability. MNF also alleviated myocardial ischemia/reperfusion injury. In cultured rodent cardiomyocytes, MNF inhibited DNA damage and cell death caused by Dox, H O or hypoxia/reoxygenation. Mechanistically, we found that MNF or another β -agonist zinterol markedly promoted heterodimerization of β -ARs with 5-HT Rs. Upregulation of the heterodimerized 5-HT Rs and β -ARs enhanced β -AR-stimulate