Identifying Irg1 inhibitors to modulate macrophage function

鉴定调节巨噬细胞功能的 Irg1 抑制剂

• 批准号: 10688965
• 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/10688965
• 关键词: Aconitic Acid; Biological Assay; Carboxy-Lyases; Cells; Citric Acid Cycle; Enzymes; Immune; Inflammatory; Pathway interactions; Role; Sampling; Therapeutic; extracellular; inhibitor; macrophage; small molecule; small molecule inhibitor; tool

"This project seeks to identify and develop small molecules that target cis-aconitate decarboxylase (Irg1, Acod1). Irg1 converts cis-aconitate (produced in the TCA cycle) into itaconate, a metabolite that has important roles in inflammatory pathways in macrophage cells. Irg1 expression and activity are elevated during M1-type polarization, resulting in increased intracellular and extracellular itaconate levels. Small molecule inhibitors of Irg1 can be used as tool molecules to further characterize the role of this enzyme in immune cells and develop compounds with therapeutic potential. During this period, the collaborative project team has explored potential high-throughput amenable assays to detect itaconate levels from cellular samples.

该项目旨在鉴定和开发针对顺式乌头酸脱羧酶（Irg 1，Acod 1）的小分子。 Irg1将顺乌头酸（在TCA循环中产生）转化为衣康酸，衣康酸是一种在巨噬细胞炎症途径中起重要作用的代谢物。 Irg1的表达和活性在M1型极化过程中升高，导致细胞内和细胞外衣康酸水平升高。 Irg1的小分子抑制剂可用作工具分子，以进一步表征这种酶在免疫细胞中的作用，并开发具有治疗潜力的化合物。 在此期间，合作项目团队探索了潜在的高通量检测方法，以检测细胞样本中的衣康酸水平。