Isolation of Inhibitors of Her-Kinase Expression (RMI)

描述（由申请人提供）：人类癌症经常表达高水平的Her家族跨膜酪氨酸激酶。其中至少一种Her2受体的过度表达与更具攻击性的行为有关。针对该受体的几种治疗策略目前处于临床开发的不同阶段。大多数已知的药物阻断或抑制Her2的活性；然而，降解这种癌蛋白可能会产生更显著的治疗效果。我们在此提出一种基于细胞的检测方法，可用于进行高通量筛选（HTS），以分离Her2激酶表达抑制剂。从这些努力中确定的化合物将代表重要的线索，将作为获得调节Her2表达的药物的起点。原则上，这些药物可以用于治疗由her2过表达/过信号驱动的晚期癌症患者。鉴于her -激酶在人类疾病中的重要性，设计和实施大规模筛选方案以鉴定her -激酶表达调节剂的时机已经成熟。据我们所知，这一目标尚未实现，我们相信，我们处于独特的地位，可以启动这一目标。

DESCRIPTION (provided by applicant): Human, cancers frequently express high levels of transmembrane tyrosine kinases of the Her family. Overexpression of at least one of these, the Her2 receptor, has been associated with a more aggressive behavior. Several therapeutic strategies targeting the receptor are now in various stages of clinical development. Most of the known agents block the activation or inhibit the activity of Her2; however, a more significant therapeutic outcome may result from degrading this oncoprotein. We propose here a cell-based assay that may be used to conduct high-throughput screens (HTS) to isolate Her2 kinase expression inhibitors. The compounds identified from these efforts will represent important leads that will serve as the starting point to obtain drugs that modulate Her2 expression. These drugs could, in principle, be used to treat patients with advanced cancers driven by Her2-overexpression/oversignalling. Given the importance of Her-kinases in human disease, the time is ripe to design and perform a large-scale screening regimen to identify Her-kinase expression modulators. To our knowledge, this has not been accomplished, and we believe that we are uniquely positioned to initiate this goal.