New paradigms for Hsp90 inhibition

90 kDa热休克蛋白（Hsp90）负责大约200种客户蛋白的成熟 底物，其中大多数与调节细胞生长的信号级联相关， 增殖因此，Hsp90抑制提供了一种治疗癌症的新方法， 通过抑制Hsp90依赖性蛋白质折叠， 过程在本申请中，我们提出开发Hsp90亚型，Grp94，Hsp90α， 和Hsp90β，使用结构引导的方法。此外，我们还将对这些产品进行并排评估， 化合物对泛抑制剂在体外和体内，以验证我们的方法。总之，这些方法 将为选择性抑制Hsp90提供新的途径，并将为抗癌提供新的范例 药物开发

The 90 kDa heat shock proteins (Hsp90) are responsible for the maturation of approximately 200 client protein substrates, most of which are associated with signaling cascades that regulate cellular growth and proliferation. Therefore, Hsp90 inhibition provides a novel approach toward the treatment of cancer as numerous signaling cascades can be derailed through inhibition of the Hsp90-dependent protein folding process. In this application, we propose to develop selective inhibitors of the Hsp90 Isoforms, Grp94, Hsp90α, and Hsp90β, using a structure-guided approach. In addition, we will perform side by side evaluation of these compounds against pan-inhibitors both in vitro and in vivo to validate our approach. Together, these methods will provide a new approach for selective inhibition of Hsp90 and will provide a new paradigm for anti-cancer drug development.