Renal Injury Prevention by SF/HGF-like Small Molecules

描述（申请人提供）：最近的研究支持散点因子/肝细胞生长因子治疗可以预防肾功能衰竭小鼠模型肾功能障碍的概念。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，我们发现利用噬菌体展示的小肽序列在体外实验中显示出SF/ hgf样血管生成活性。通过计算机建模，我们已经在许多体外和体内实验中发现了一种具有SF/ hgf样活性的小分子化合物。小规模的初步研究表明，这种小分子化合物可能具有类似于SF/HGF的保护作用。本实验将通过确定其在肾功能衰竭小鼠模型中保存肾功能的有效性来扩展这些研究。这些研究预计将为更深入的II期研究提供足够的支持数据，目标是将该化合物（或其他更有效或更容易交付的化合物）用于肾衰竭的临床试验。

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.