Development of nuclear receptors as anthelmintic targets

描述(申请人提供)：全球有超过10亿人 被寄生线虫感染，这种线虫会导致各种衰弱的营养物质， 胃肠道等疾病。许多这样的感染是无法治愈的 现有的药物和预防性疫苗对这些人还不可行 复杂的寄生虫。该项目的长期目标是确定新的 能够满足人类健康需求的抗线虫化合物。核子 受体(NR)转录因子是已证实的有效和 商业上成功的药物和杀虫剂，但尚未开发 作为驱虫药的靶标。选择性地干扰药物的化合物 线虫生存所必需的NRs功能将为线虫的 控制人体重要寄生虫的新型驱虫剂的研究进展 线虫感染。I期鉴定寄生线虫的结果 在线虫中具有基本功能的NRS的同源基因，并建立了 基于细胞的线虫NR活性化学调节剂的测定。第二阶段将 利用在第一阶段获得的知识和工具来部署专有 用于分离改变线虫的化合物的高通量筛选电池 天然橡胶功能。将使用二次化验来选择这些活性化合物 最有希望在第三阶段进一步发展的项目。 建议的商业应用：不可用

DESCRIPTION (Provided by applicant): Over one billion people worldwide are infected by parasitic nematodes that cause various debilitating nutritional, gastrointestinal, and other diseases. Many such infections are not curable with existing medications, and preventive vaccines are not yet feasible for these complex parasites. The long-term goal of this project is to identify new anti-nematode compounds that will fulfill this human health need. Nuclear receptor (NR) transcription factors are proven targets of effective and commercially successful drugs and insecticides, but have not yet been exploited as anthelmintic targets. Compounds that selectively interfere with the functions of NRs essential for nematode viability will provide leads for the development of novel anthelmintics for the control of important human parasitic nematode infections. The results of Phase I identified parasitic nematode orthologs of NRs that have essential functions in C. elegans and established a cell-based assay for chemical modulators of nematode NR activity. Phase II will exploit the knowledge and tools acquired during Phase I to deploy a proprietary battery of high-throughput screens for isolating compounds that alter nematode NR function. Secondary assays will be used to select those active compounds that are most promising for further development in Phase III. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE