课题基金 / 基金详情

Second-Generation Novel Liver Stage Active Antimalarials

Second-Generation Novel Liver Stage Active Antimalarials
第二代新型肝期活性抗疟药
批准号:
10180516
负责人:
JANE X KELLY
金额:
$68.15万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-04-01 至 2026-03-31

项目摘要

项目成果

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中文摘要
翻译
项目总结/摘要 尽管为消灭疟疾作出了广泛努力,但疟疾的全球影响仍然令人震惊。我们 已经开发了一种新的抗疟疾吖啶酮化学型,其对肝脏阶段和 血液期疟疾,以及单剂治愈能力和预防复发感染的潜力。的能力 对抗感染的多个阶段是一个强大的工具,一个理想的适合实现 随着消灭疟疾工作的开展,严格的优化过程 生产了一系列第二代吖啶酮,在功效,代谢稳定性, 药代动力学和安全性特征。我们的首要目标是开发一种新的抗疟疾药物, 患有G6 PD缺乏症的人,以及最脆弱的人群-孕妇和儿童, 支持在世界范围内消灭这种疾病。该项目的具体目标是引导 优化研究,以生产第二代候选药物,用于全面的临床前评价, 具有广谱特性,并显示出增强的疗效、安全性、溶解度和代谢/药代动力学 调查对选定的吖啶酮候选药物的耐药性倾向,并确定 通过全基因组测序和分析确定分子靶点;并探索这些靶点的作用方式 使用功能测定和生物分析方法的肝阶段活性抗疟吖啶酮。
英文摘要
PROJECT SUMMARY/ABSTRACT The global impact of malaria remains staggering despite extensive efforts to eradicate the disease. We have developed a novel antimalarial acridone chemotype with dual stage efficacy against both liver stage and blood stage malaria, as well as single-dose cure ability and potential to prevent relapsing infection. The ability to combat multiple stages of the infection represents a powerful tool, and one ideally suited to achieve the broadest possible benefit as the malaria eradication effort proceeds. A rigorous optimization process has produced a series of second-generation acridones with significant improvements in efficacy, metabolic stability, pharmacokinetics, and safety profiles. Our overarching goal is to develop a novel antimalarial that is safe in individuals with G6PD deficiency, and in the most vulnerable populations – pregnant women and children, thus supporting world-wide elimination of the disease. The specific goal of this project is to conduct lead optimization studies to produce second-generation candidates for full preclinical evaluation that retain the broad-spectrum features and demonstrate enhanced efficacy, safety, solubility, and metabolic/pharmacokinetic profiles; to investigate the propensity for drug resistance to selected acridone candidates and identify the molecular target(s) through whole genome sequencing and analysis; and to explore mode(s) of action for these liver stage active antimalarial acridones using functional assays and bioanalytical approaches.
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会议论文
Natural Product Inspired Novel Antimalarials with Radical Cure Potential
  • 批准号:
    10635649
  • 项目类别:
  • 资助金额:
    $65.64万
  • 财政年份:
    2023
  • 负责人:
    JANE X KELLY
  • 依托单位:
Novel Synergistic Antimalarials with Resistance Reversal Function
  • 批准号:
    10534667
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2022
  • 负责人:
    JANE X KELLY
  • 依托单位:
Novel Synergistic Antimalarials with Resistance Reversal Function
  • 批准号:
    10368441
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2022
  • 负责人:
    JANE X KELLY
  • 依托单位:
Second-Generation Novel Liver Stage Active Antimalarials
  • 批准号:
    10583479
  • 项目类别:
  • 资助金额:
    $65.97万
  • 财政年份:
    2021
  • 负责人:
    JANE X KELLY
  • 依托单位:
海外基金