Small Molecule Therapeutics for Myocardial Ischemia

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DESCRIPTION (provided by applicant): Left untreated, myocardial ischemia can lead to cardiomyocte death and pump failure. In fact, ischemic heart disease is a significant cause of morbidity and mortality in the U.S. Recent evidence suggests that scatter factor / hepatocyte growth factor, exerts direct protective effects on cardiac myocytes and can potentially be used for salvage of the ischemic myocardium. However the feasibility of using this growth factor in the form of gene or protein therapy is compounded by numerous logistical issues. Using a product discovery engine comprising phage display, 3-dimensional molecular modeling, protein chemistry and preclinical biology, Angion successfully identified an organic small molecule mimetic of scatter factor. We have since identified a library of compounds based on the Refanalin structure that are potential scatter factor mimetics. The present Phase I application couples a targeted proteomics approach with efficacy studies to identify a small molecule pharmacophore within this library that mimics the effects of scatter factor on the cardiac myocyte and protects against myocardial infarction. The lead candidate emerging from these studies will be submitted to in-depth Phase II studies with the ultimate objective of using a small molecule mimetic of scatter factor for salvage of the ischemic myocardium.