RENAL INJURY PREVENTION BY SF/HGF-LIKE SMALL MOLECULES

DESCRIPTION (provided by applicant): Recent studies support the concept that treatment with scatter factor/hepatocyte growth factor can prevent renal dysfunction in mouse models of renal failure. SF/HGF has multiple actions such as proliferative, pro-fibrinolytic and anti-apoptotic activities that may contribute to this protective function. Recently we have discovered small peptide sequences using phage display that demonstrate SF/HGF-like angiogenic activity in in vitro assays. Using computer modeling we have identified a small molecule compound that has SF/HGF-tike activity in numerous in vitro and in vivo assays. Small pilot studies suggest that this small molecule compound may have protective actions similar to SF/HGF. The experiments in the current proposal will extend these studies by determining its effectiveness in preserving renal function in mouse models of renal failure. These studies are expected to provide sufficient supporting data for more in depth Phase II studies with the goal of bringing this compound (or other more potent or easily deliverable compounds) into clinical trials for renal failure.