High-throughput screening to identify inhibitors of breast-to-brain metastasis

高通量筛选以确定乳腺至脑转移的抑制剂

• 批准号: 10916047
• 负责人: Mark Henderson
• 金额: $ 24.08万
• 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/10916047
• 关键词: Automobile Driving; Basic Science; Biological Assay; Brain; Breast; Breast Epithelial Cells; Cells; Drug Kinetics; Health; Human; Human Genome; Metastatic malignant neoplasm to brain; National Center for Advancing Translational Sciences; Rare Diseases; Research; Route; Toxic effect; Translations; brain cell; drug candidate; efficacy study; high throughput screening; improved; in vivo; inhibitor; interest; novel; pharmacologic; programs; small molecule; tool

During this period, the collaborative team performed high-throughput screening to identify small molecules that selectively kill breast-to-brain metastatic cells relative to normal breast epithelial cells. Several compounds of interest emerged, which were advanced to pharmacokinetic studies to characterize brain exposure and select route of administration. In vivo efficacy studies are currently underway. Additionally, the team developed a matrix assay to identify small molecule combinations which display synergistic toxicity against brain-metastatic cells. Several combination screens have been performed and the team is assessing options for advancing to efficacy studies.

在此期间，合作团队进行了高通量筛选，以识别相对于正常乳腺上皮细胞选择性地杀死乳房到脑转移细胞的小分子。出现了几种感兴趣的化合物，这些化合物被推进到药代动力学研究，以表征脑暴露和选择给药途径。体内疗效研究目前正在进行中。此外，该团队还开发了一种基质试验，以确定对脑转移细胞显示协同毒性的小分子组合。已经进行了几次联合筛查，研究小组正在评估进入疗效研究的各种选择。