qHTS to Identify Activators and Inhibitors of Wip1

qHTS 鉴定 Wip1 激活剂和抑制剂

• 批准号: 10004989
• 负责人: Matthew Hall
• 金额: $ 4.76万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10004989
• 关键词: Apoptotic; Biological Assay; Cells; Chemicals; Clinical; Collection; DNA Damage; Environment; Family; Human; Malignant Neoplasms; PPM1D gene; Pharmaceutical Chemistry; Pharmacologic Substance; Protein Serine/Threonine Phosphatase; Proteins; TP53 gene; anticancer treatment; base; enzyme mechanism; high throughput screening; inhibitor/antagonist; member; novel; outcome forecast; overexpression; protein phosphatase 2C; response; small molecule; therapeutic development; tumor growth

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.

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，项目团队开发并验证了适合高通量筛选的Wip1活性测定。Wip1活性测定通过NCATS药物收集的定量高通量筛选进行验证。经验证的检测方法正用于高通量筛选整个NCATS收集的小分子。其他基于细胞的活性测定也得到了优化和验证。额外的努力集中在酶作用机制的详细机理研究上，这可以在化学先导物的药物化学优化期间利用。