A Novel Cell-Based Assay to Identify Small Molecules for Galactocerebrosidase (GALC)

一种新型的基于细胞的半乳糖脑苷酶 (GALC) 小分子鉴定方法

• 批准号: 10688941
• 负责人: Mark Henderson
• 金额: $ 14.62万
• 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/10688941
• 关键词: Biological Assay; Cells; Collaborations; Communities; Development; Disease; Enhancers; Extramural Activities; Fibroblasts; Fostering; General Population; Globoid cell leukodystrophy; Goals; Human; Informatics; Lipids; Modeling; National Center for Advancing Translational Sciences; Neurologic; Oligodendroglia; Patients; Pharmaceutical Chemistry; Pharmaceutical Preparations; Process; Publications; Research; Research Personnel; Residual state; Resources; Training; Translations; United States National Institutes of Health; Work; analog; base; drug discovery; galactosylceramidase; high throughput screening; human disease; improved; mutant; novel; novel therapeutics; screening; small molecule; small molecule therapeutics; therapeutic development

During this period, the collaborative team has worked to validate and characterize hit compounds previously identified in the primary GALC screen. SAR studies are ongoing, alongside the development of a qHTS assay using MS and human krabbe oligodendrocytes (produced by reprogramming patient fibroblast). This assay will allow the quantification of lipid reduction upon treatment with analogs of hit molecules. As a center, the Early Translation Branch (ETB) has fostered and maintained over 110 active collaborations with both NIH and extramural investigators, facilitating drug discovery efforts across the entire spectrum of human disease. These efforts have led to dozens of high-throughput screens and a number of medicinal chemistry campaigns to further improve on screening hits, providing our collaborators and the general research community with publications and a variety of promising small molecule probes and leads. In addition, the ETB has worked to advance a number of informatics initiatives to make better use of existing drug and disease target information and provide the general public with easily accessible resources, further catalyzing the development of new therapies for human disease.

在此期间，合作团队一直致力于验证和表征先前在初级GALC筛选中确定的hit化合物。