Glycolysis-activating small molecule cocktail for myocardial infarction

Activating a cardiomyocyte switch from oxidative phosphorylation to glycolysis via a small molecule cocktail could help treat myocardial infarction. High-throughput screening of 11,000 compounds in primary rat cardiomyocytes, followed by computational prediction of small molecule interactions, identified five compounds — targeting ADRA1, MCT1, PTEN, JAK-1 and the DYRK family of kinases — that when combined induced cell cycle re-entry and cytokinesis in mouse, rat and human cardiomyocytes.

In mouse and rat models of myocardial infarction, the cocktail increased cardiomyocyte proliferation compared with vehicle. In a rat model of myocardial injury, the compounds increased cardiomyocyte proliferation, blood vessel count, and blood flow from the infarcted left ventricle, and decreased cardiac fibrosis and fractional shortening compared with vehicle. ...