Identification of modulators of PLK1

PLK1 调节剂的鉴定

• 批准号: 10011399
• 负责人: Anton Simeonov
• 金额: $ 25.03万
• 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/10011399
• 关键词: Adopted; Biological Assay; Cells; Collaborations; Crystallization; Goals; In Vitro; Malignant Neoplasms; Manuscripts; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; PLK1 gene; Pharmaceutical Chemistry; Preparation; Property; Role; Structure; Toxic effect; Work; anti-cancer therapeutic; base; design; improved; in vivo; in vivo Model; pharmacokinetics and pharmacodynamics; screening; small molecule; small molecule inhibitor; virtual

The project team aims to identify small molecule inhibitors capable of targeting the PBD domain of PLK1. Optimized compounds will be extensively profiled to identify candidates with appropriate potency, selectivity, and pharmacokinetic (PK)/pharmacodynamic (PD) profile to enable their use in both in vitro and in vivo models. During this period, the project team worked to develop cell-based assays to monitor PLK1-PBD activity in live cells, and identified small molecule hits using virtual screening. A medicinal chemistry optimization campaign is ongoing to further improve compound properties. We have adopted a cell based nanoBret assay to support currently ongoing hit optimization. A manuscript is under preparation in collaboration with Kyung Lee (NCI) and Ken Jacobson (NIDDK). Medicinal chemistry still underway to identify the probe compound which can be used in vivo study.

该项目团队旨在鉴定能够靶向 PLK1 PBD 结构域的小分子抑制剂。优化的化合物将被广泛分析，以确定具有适当效力、选择性和药代动力学 (PK)/药效学 (PD) 特征的候选化合物，从而使其能够在体外和体内模型中使用。在此期间，项目团队致力于开发基于细胞的检测方法来监测活细胞中的 PLK1-PBD 活性，并使用虚拟筛选来识别小分子命中。药物化学优化活动正在进行中，以进一步改善化合物特性。 我们采用了基于细胞的 nanoBret 测定来支持当前正在进行的命中优化。正在与 Kyung Lee (NCI) 和 Ken Jacobson (NIDDK) 合作准备一份手稿。药物化学仍在进行中，以确定可用于体内研究的探针化合物。