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Abstract
Grant Number: 5R44AI048937-03 PI Name: SLUDER, ANN E. PI Email: asluder@cambriabio.com PI Title: DIRECTOR, GENETICS Project Title: Development of nuclear receptors as anthelmintic targets Abstract: 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
Thesaurus Terms:
anthelmintic, drug discovery /isolation, drug screening /evaluation, nuclear receptor
binding site, chimeric protein, fungal genetics, genetic transcription, ligand
Caenorhabditis elegans, bioassay, high throughput technology
Institution: CAMBRIA BIOSCIENCES, LLC 8A HENSHAW ST WOBURN, MA 01801 Fiscal Year: 2003 Department: Project Start: 01-MAR-2001 Project End: 30-JUN-2004 ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES IRG: ZRG1
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