IMB-10189721, a novel first-in-class partial fatty acid oxidation (pFOX) inhibitor improves cardiac remodelling and function post-myocardial infarction.
Myocardial fatty acid (FA) and glucose metabolism are tightly regulated in health to meet high energy demand. Dysregulation occurs in acute ischemia (reliance on anaerobic glycolysis) while there is a marked increase in mitochondrial FA oxidation during reperfusion. In heart failure (HF) glycolysis is partially uncoupled from glucose oxidation due to reduced pyruvate dehydrogenase (PDH) activity, reducing the efficiency of energy generation. FA metabolism yields ~20% less ATP than glucose for the same O2 consumption. Thus, inhibition of FA oxidation shifts metabolism toward glucose, increasing PDH activity and the efficiency of ATP generation. We examined the ability of IMB-1018972 (IMB-101) a novel partial FA oxidation (pFOX) inhibitor to mitigate left ventricular (LV) dysfunction and remodelling after myocardial infarction (MI).
M.Harding et al. American College of Cardiology 2021