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Identification of small molecule degraders of XPB for inflammatory diseases

Identification of small molecule degraders of XPB for inflammatory diseases
炎症性疾病 XPB 小分子降解剂的鉴定
批准号：
10916058
负责人：
Mark Henderson
金额：
$12.58万
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/10916058
关键词：
AffinityAutomobile DrivingBasic ScienceDiseaseERCC3 geneHealthHumanHuman GenomeInflammatoryMethodsNational Center for Advancing Translational SciencesNuclear ProteinPhenocopyProductionProteinsProteomicsRare DiseasesResearchSpironolactoneTranslationscytokinedrug candidatehigh throughput screeningimprovedinterestpharmacologicprogramsscreeningsmall moleculetool

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中文摘要
翻译
这个合作团队的目标是在以前研究的基础上，通过识别小分子来复制螺内酯对XPB蛋白质稳定性的影响。XPB是一种核蛋白，调节炎性细胞因子的产生。 在此期间，合作团队完成了对8000多个生物活性分子的高通量筛选，以确定导致XPB蛋白降解的化合物。从筛选中发现了几种感兴趣的化合物，这些化合物正在进一步表征。此外，使用基于亲和力的探针和蛋白质组学方法相结合的方法研究了顶层活性物质的作用机制。
英文摘要
This collaborative team aims to build on previous research by identifying small molecules that phenocopy the effect of spironolactone on XPB protein stability. XPB is a nuclear protein that regulates the production of inflammatory cytokines. During this period, the collaborative team completed high-throughput screening of more than 8,000 biologically active molecules to identify compounds that induce degradation of the XPB protein. Several compounds of interest emerged from screening, which are being further characterized. Additionally, the mechanism of action of top actives were examined using several approaches combining affinity-based probes and proteomic methods.
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