Development of a novel nematode/Wolbachia target

新型线虫/沃尔巴克氏体靶标的开发

• 批准号: 6831911
• 负责人: CLOTILDE CARLOW
• 金额: $ 9.75万
• 依托单位: NEW ENGLAND BIOLABS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831911
• 关键词: Caenorhabditis elegans; Filarioidae; Nematoda; Rickettsiales; Wuchereria; anthelmintics; drug design /synthesis /production; drug discovery /isolation; drug receptors; drug screening /evaluation; enzyme inhibitors; helminthiasis; high throughput technology; molecular cloning; nucleic acid sequence; phosphoglycerate mutase; protein quantitation /detection; recombinant proteins; symbiosis

DESCRIPTION (provided by applicant): Parasitic nematodes are responsible for a number of severe diseases in humans and animals. Approximately $600 million is spent each year in drugs to treat nematode infections in animals. These drugs are not completely effective so the discovery of new therapies and drug targets is of paramount importance. Recently we employed a novel bioinformatics approach to identify valid drug targets in nematodes that are absent from mammals. A particularly promising target has been discovered and validated which merits further development and inclusion in high throughput screens for the identification of inhibitors that will serve as new drug leads. Phase I of this project includes further characterization and large-scale production of recombinant target isolated from several nematodes and their endosymbiotic bacteria Wolbachia. In addition, high throughput screens will be developed and established for the screening of inhibitors. Some preliminary screening may begin in Phase I. Phase II of the project will involve screening proprietary compound libraries and the selection of the best candidates for optimization and further testing in appropriate in vivo systems.

描述（由申请人提供）：寄生线虫导致人类和动物的许多严重疾病。每年大约花费 6 亿美元用于治疗动物线虫感染的药物。这些药物并不完全有效，因此发现新疗法和药物靶点至关重要。最近，我们采用了一种新颖的生物信息学方法来识别哺乳动物中不存在的线虫中的有效药物靶点。已经发现并验证了一个特别有前途的靶点，值得进一步开发并纳入高通量筛选中，以鉴定将作为新药物先导物的抑制剂。该项目的第一阶段包括进一步表征和大规模生产从几种线虫及其内共生细菌沃尔巴克氏体中分离的重组靶标。此外，还将开发和建立高通量筛选来筛选抑制剂。一些初步筛选可能会在第一阶段开始。该项目的第二阶段将涉及筛选专有化合物库以及选择最佳候选化合物以在适当的体内系统中进行优化和进一步测试。