Development of nuclear receptors as anthelmintic targets

描述（由申请人提供）：全球有超过10亿人 被寄生线虫感染，引起各种使人衰弱的营养， 胃肠道和其他疾病。许多这样的感染是不可治愈的， 现有的药物和预防性疫苗对这些人来说还不可行。 复杂的寄生虫该项目的长期目标是确定新的 抗线虫化合物，将满足这一人类健康的需要。核 受体（NR）转录因子被证明是有效的靶点， 商业上成功的药物和杀虫剂，但尚未开发 作为驱虫的目标。选择性地干扰 NRs对线虫生存力至关重要的功能将为线虫的生长提供线索。 防治人体重要寄生虫病的新型驱虫药的研制 线虫感染I期鉴定结果寄生线虫 在C.并建立了一个 线虫NR活性的化学调节剂的基于细胞的测定。二期将 利用第一阶段获得的知识和工具来部署专有的 用于分离改变线虫的化合物的一组高通量筛选 NR功能。将使用二级试验来选择这些活性化合物 这是最有希望在第三阶段进一步发展。 拟议商业应用：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