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Identifying Irg1 inhibitors to modulate macrophage function

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
项目类别：
财政年份：
--
资助国家：
美国
项目状态：
未结题
起止时间：
至
来源：
https://reporter.nih.gov/project-details/10688965
关键词：
Aconitic AcidBiological AssayCarboxy-LyasesCellsCitric Acid CycleEnzymesImmuneInflammatoryPathway interactionsRoleSamplingTherapeuticextracellularinhibitormacrophagesmall moleculesmall molecule inhibitortool

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中文摘要
翻译
这个项目致力于识别和开发针对顺式乌头酸脱羧酶(IRG1，Acod1)的小分子。IRG1将顺式乌头酸(在TCA循环中产生)转化为衣康酸，这是一种在巨噬细胞炎症途径中发挥重要作用的代谢物。在M1型极化过程中，IRG1的表达和活性增加，导致细胞内和细胞外衣康酸水平增加。IRG1的小分子抑制物可用作工具分子，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从细胞样本中检测衣康酸水平的潜在高通量顺应性分析方法。
英文摘要
"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.
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