Renal Injury Prevention by SF/HGF-like Small Molecules

描述（由申请方提供）：最近的研究支持以下概念：在肾衰竭小鼠模型中，使用分散因子/肝细胞生长因子治疗可以预防肾功能障碍。SF/HGF具有多种作用，如增殖、促纤溶和抗凋亡活性，可能有助于这种保护功能。最近，我们已经发现了小肽序列使用噬菌体展示，证明SF/HGF样血管生成活性在体外试验。使用计算机建模，我们在许多体外和体内试验中鉴定出了一种具有SF/HGF样活性的小分子化合物。小型试点研究表明，这种小分子化合物可能具有类似于SF/HGF的保护作用。本提案中的实验将通过确定其在肾衰竭小鼠模型中保留肾功能的有效性来扩展这些研究。预计这些研究将为更深入的II期研究提供足够的支持数据，目的是将该化合物（或其他更有效或更容易递送的化合物）纳入肾衰竭的临床试验。

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.