qHTS to Identify Activators and Inhibitors of Wip1

该项目的总体目标是开发有效的、选择性的和生物活性的Wip1小分子调节剂，用作化学探针和治疗开发的起点。 在此期间，项目组开发并验证了一种可用于高通量筛选的Wip1活性检测方法。Wip1活性测定通过对NCATS药物收藏进行定量高通量筛选而得到验证。这种经过验证的检测方法正用于对整个NCATS收集的小分子进行高通量筛选。其他基于细胞的活性分析也得到了优化和验证。更多的努力集中在酶作用机制的详细机制研究上，这些机制可以在化学先导的药物化学优化过程中加以利用。

The overall objective of this project is to develop potent, selective, and bioactive small molecule modulators of Wip1 for use as chemical probes and starting points for therapeutic development. During this period, the project team developed and validated a Wip1 activity assay amenable for high-throughput screening. The Wip1 activity assay was validated by quantitative high-throughput screening of the NCATS pharmaceutical collection. The validated assay is being used for high-throughput screening of the entire NCATS collection of small molecules. Other cell-based activity assays have also been optimized and validated. Additional efforts have focused on detailed mechanistic studies of the enzymes mechanism of action, which could be exploited during medicinal chemistry optimization of chemical leads.