Masaomi Umeda

Discovery of novel and selective IKK-β serine-threonine protein kinase inhibitors. Part 1

IkappaB kinase beta (IKK-beta) is a serine-threonine protein kinase critically involved in the activation of the transcription factor Nuclear Factor kappa B (NF-kappaB) in response to various inflammatory stimuli. We have identified a small molecule inhibitor of IKK-beta. Optimization of the lead compound resulted in improvements in both in vitro and in vivo potency, and provided IKK-beta inhibitors exhibiting potent activity in an acute cytokine release model (LPS-induced TNFalpha).

Improvement of ischemic myocardial dysfunction by nisoldipine

SummaryWe examined the cardioprotective effect of nisoldipine against myocardial dysfunction during ischemia and reperfusion in Langendorff perfused rabbit hearts. Nisoldipine was administered to the hearts before 60 minutes of global ischemia. This agent inhibited the increase of end-diastolic pressure during ischemia and also improved the recovery of left ventricular developed pressure and coronary flow during reperfusion in a concentration-dependent manner. The maximal cardioprotective effect was observed in 10−8 M nisoldipine. The beneficial effect was associated with an increase of coronary flow during reperfusion. Therefore, both the nisoldipine-increased coronary flow during reperfusion and the inhibition of ischemic contracture by nisoldipine seem to play a crucial role in improving myocardial dysfunction of ischemic-reperfused hearts.