qHTS to Identify Activators and Inhibitors of Wip1

qHTS 鉴定 Wip1 激活剂和抑制剂

• 批准号: 10255280
• 负责人: Matthew Hall
• 金额: $ 11.24万
• 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/10255280
• 关键词: Apoptotic; Binding; Biological Assay; Chemicals; Clinical; DNA Damage; Environment; Family; Fluorescence; Human; Libraries; Malignant Neoplasms; Mass Spectrum Analysis; PPM1D gene; Pharmaceutical Chemistry; Powder dose form; Protein Serine/Threonine Phosphatase; Proteins; Reporter; Surface Plasmon Resonance; TP53 gene; anticancer treatment; enzyme mechanism; high throughput screening; inhibitor/antagonist; member; novel; outcome forecast; overexpression; protein phosphatase 2C; response; screening; small molecule; small molecule libraries; 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 performed high-throughput screening against NCATS annotated libraries and diverse chemical library using a RapidFire mass spectrometry assay. The primary screening hits were further evaluated by a variety of additional assays to characterize their activities, including fluorescence reporter orthogonal assay, and binding studies by surface plasmon resonance (SPR). Currently powder order has been placed for the top ranking chemotypes/singletons and 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、生物活性的Wip1小分子调节剂，作为化学探针和治疗开发的起点。