MT2, a NGF-mimetic compound, decreases myocardial damage induced by ischemia/reperfusion injury

Recent studies in experimental models of acute myocardial ischemia demonstrated the protective role of NGF in heart injury. The protective activity exerted by NGF is mainly based on the anti-apoptotic properties of the neurotrophin which are exercised on cardiomyocytes and endothelial cells of the myocardium following ischemia/reperfusion injury. Unfortunately, the use of NGF as therapeutic tool in ischemia/reperfusion injury would not be recommended due to its sensitivity to proteolysis. We obtained neurotrophin mimetics through the functional screening of a chemical library of compounds with spatial coordinates fitting the NGF binding site on TrkA molecule. The extensive biochemical and functional characterization of them revealed that they were endowed with NGF mimetic properties and interact with TrkA receptors. In particular, the selected compound MT2 interacts with TrkA with a Kd of 100nM and inhibits the apoptotic process induced by metabolic stress several cell types. We therefore evaluated the effect of MT2 in in vitro and in vivo models of myocardial damage induced by ischemia/reperfusion injury.