Identification of small molecule inhibitors of miR-155 expression in Th17 cells

Th17细胞中miR-155表达的小分子抑制剂的鉴定

• 批准号: 10005785
• 负责人: Marc Ferrer-Alegre
• 金额: $ 13.27万
• 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/10005785
• 关键词: Autoimmune Diseases; Biological Assay; Biology; Cells; Chemicals; Collaborations; Crohn' s disease; Disease; Experimental Autoimmune Encephalomyelitis; Extramural Activities; Genomics; Goals; Informatics; Modeling; Multiple Sclerosis; Pharmaceutical Chemistry; Phenotype; Process; Production; Psoriasis; Research; Research Personnel; Synthesis Chemistry; Testing; United States National Institutes of Health; Validation; Work; assay development; base; drug development; drug discovery; inhibitor/antagonist; lead optimization; mouse model; new technology; novel; screening; small molecule; small molecule inhibitor; small molecule therapeutics; therapeutic development; tool

During this period, the project team worked to validate and characterize hit compounds identified in the previously completed primary miR-155 screen. Compounds were confirmed for their ability to down-regulate Il-17 production in functional assays using primary cells. Select hit molecules have been advanced toward testing in EAE, a mouse model for multiple sclerosis. Following additional characterization and validation, molecules with promising activity profiles may hold promise for the treatment of autoimmune diseases like multiple sclerosis, Crohn's disease and psoriasis.

在此期间，项目组致力于验证和表征在之前完成的初级miR-155筛查中确定的命中化合物。在使用原代细胞的功能分析中，化合物被证实有能力下调IL-17的产生。选定的HIT分子已经在多发性硬化症的小鼠模型EAE中进行了测试。经过进一步的表征和验证，具有良好活性的分子可能有望用于多发性硬化症、克罗恩病和牛皮癣等自身免疫性疾病的治疗。