High Throughput Screening for Biased Agonists of the TSH Receptor that Activate the Beta-arrestin pathway

高通量筛选激活 β-抑制蛋白途径的 TSH 受体偏向激动剂

• 批准号: 10255292
• 负责人: Juan Marugan
• 金额: $ 30.57万
• 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/10255292
• 关键词: Agonist; Arrestin Beta 1; Biology; Cell Line; Collaborations; Disease; Extramural Activities; Goals; Informatics; Modeling; Pathway interactions; Pharmaceutical Chemistry; Phenotype; Process; Research; Research Personnel; Series; Signal Transduction; Synthesis Chemistry; Testing; Thyrotropin Receptor; Translations; United States National Institutes of Health; Validation; Work; analog; assay development; base; beta-arrestin; drug development; drug discovery; follow-up; high throughput screening; lead optimization; new technology; novel; overexpression; screening; small molecule; small molecule therapeutics; therapeutic development; tool

The main goal of this project is to develop a potent and selective small molecule TSHR agonist, with biased signaling profile. During this period, the most promising hits from high-throughput screening were identified and followed up with medicinal chemistry and several series of analogs were synthesized. Candidates with attractive activity profiles were pursued with medicinal chemistry to synthesize a series of new analogs, which were advanced for testing in a TSHR overexpressing cell line to determine beta-Arrestin 1 signaling.

该项目的主要目标是开发一种有效的、选择性的小分子 TSHR 激动剂，具有偏向的信号传导特征。 在此期间，通过高通量筛选鉴定出最有希望的命中产物，并进行药物化学跟踪，并合成了几个系列的类似物。通过药物化学寻找具有有吸引力的活性特征的候选物，以合成一系列新的类似物，这些类似物随后在 TSHR 过表达细胞系中进行测试，以确定 β-Arrestin 1 信号传导。