Identify inhibitors of the Six1/Eya interaction using high throughput screening

描述(申请人提供)：SIX1是一种发育基因，在很大比例的乳腺癌中异常重新表达。这种过度表达在乳腺癌的发生和转移发展中起着因果作用。由于SIX1没有自己的激活或抑制结构域，Eya家族的SIX1共激活蛋白在SIX1介导的乳腺肿瘤的发生和转移中是必不可少的。我们已经开发了一种基于AlphaScreen的针对SIX1/Eya相互作用的HTS分析方法。我们建议使用NIH MLPCN化合物进行大规模高通量筛选，以确定SIX1/EYA相互作用的抑制剂。我们计划测试这些抑制剂作为治疗工具的潜力，以抑制SIX1介导的乳腺肿瘤发生和转移。这些抑制剂也可以作为有价值的化学探针用于涉及SIX1/EYA相互作用的研究。

DESCRIPTION (provided by applicant): Six1 is a developmental gene that is abnormally re-expressed in a large percentage of breast cancers. This over-expression plays a causal role in the initiation and metastatic development of breast cancers. Since Six1 does not have its own activation or repression domain, the Eya family of Six1 co-activator proteins is essential for Six1-mediated breast tumorigenesis and metastasis. We have developed an AlphaScreen based HTS assay targeting the Six1/Eya interaction. We propose to perform a large scale high throughput screening using the NIH MLPCN compounds to identify inhibitors of the Six1/Eya interaction. We plan to test these inhibitors for their potential as therapeutic tools to inhibit Six1-mediated breast tumorigenesis and metastasis. These inhibitors can also be used as valuable chemical probes for studies involving the Six1/Eya interaction.