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Development of the potent anti-malarial and anti-Toxoplasma drug, ELQ-316

Development of the potent anti-malarial and anti-Toxoplasma drug, ELQ-316
开发强效抗疟疾和抗弓形虫药物 ELQ-316
批准号:
8810588
负责人:
Joseph Stone Doggett
金额:
$0.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-01-01 至 2018-12-31

项目摘要

项目成果

Joseph Stone Doggett的其他基金

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中文摘要
翻译
疟疾是世界上导致死亡的主要原因之一。目前对疟疾的治疗受到药物的限制
英文摘要
Malaria is one of the leading causes of mortality in the world. Current therapy for malaria is limited by drug resistance. Toxoplasma gondii is found worldwide and causes devastating eye disease and encephalitis. Current therapy for toxoplasmosis is poorly tolerated and does not eradicate infection from its host. Veterans are exposed to these infections during their military service and new treatments would greatly improve veterans' health. Dr. Doggett and his colleagues have developed new drugs, endochin like quinolones (ELQ), that are highly effective against malaria and T. gondii. He has chosen ELQ-316 as a lead drug because it is orally available, non-toxic and highly effective. Dr. Doggett's preliminary studies in T. gondii and Saccharomyces cerevisiae suggest that ELQs inhibit the mitochondrial cytochrome bc1 complex (cyt bc1). Dr. Doggett will test the hypothesis that ELQ-316 inhibits cyt bc1 and characterize how ELQ-316 interacts with the cyt bc1. He will also test if inhibiting both active sites of cyt bc1 reduces P. falciparum's ability to develop drug resistance. Dr. Doggett will test this hypothesis by measuring the rate of resistance against the combination of ELQ-316 with atovaquone and the rate of resistance of ELQ-316 against a P. falciparum clone that has atovaquone resistance. If mutations occur in both cyt bc1 active sites, he will measure the catalytic activity of the enzyme. Dr. Doggett will optimize the administration of ELQ-316 by finding synergistic combinations of ELQ-316 with clinically used drugs against toxoplasmosis and malaria, determining the pharmacokinetics of ELQ-316 orally and transdermally, and developing an ELQ-316 prodrug. Dr. Doggett is an infectious disease physician at Oregon Health & Sciences University and the Portland VA Medical Center. He is specifically interested in new treatments for neglected tropical diseases that effect veterans. He has carried out research in Dr. Mike Riscoe's lab investigating drug mechanism of action and drug resistance in protozoan pathogens. Dr. Doggett has developed proficiency in the biochemical and molecular methods that are needed for his current research plan. The VA CDA-2 award will provide Dr. Doggett further training in drug mechanism and new training in pharmacokinetics, drug design and computer based molecular modeling. As a part of a robust training plan, Dr. Doggett has selected a panel of senior scientists with expertise in molecular parasitology, T. gondii, Plasmodia, preclinical drug development and S. cerevesiae as a model system. This panel is experienced in mentoring early investigators and will meet with Dr. Doggett formally every 6 months. The panel will provide advice regarding experiments, publications and career development. In addition, Dr. Doggett will attend the Woods Hole molecular parasitology course, attend science courses at OHSU and present his research at conferences. This award will culminate in the establishment of Dr. Doggett's independently funded lab devoted to anti-protozoan drug discovery for veterans and his infectious disease career as a physician with parasitology expertise devoted to the care of veterans.
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COVID19: Optimized Endosome-Targeting Compounds for SARS-CoV-2 and Emerging Coronaviruses
  • 批准号:
    10155164
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2021
  • 负责人:
    Joseph Stone Doggett
  • 依托单位:
COVID19: Optimized Endosome-Targeting Compounds for SARS-CoV-2 and Emerging Coronaviruses
  • 批准号:
    10359085
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2021
  • 负责人:
    Joseph Stone Doggett
  • 依托单位:
Advanced Preclinical Testing of a Broad-Spectrum Antiparasitic Quinolones for Veteran Health
  • 批准号:
    10265392
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2019
  • 负责人:
    Joseph Stone Doggett
  • 依托单位:
Advanced Preclinical Testing of a Broad-Spectrum Antiparasitic Quinolones for Veteran Health
  • 批准号:
    10454872
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2019
  • 负责人:
    Joseph Stone Doggett
  • 依托单位:
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