Proteasome inhibitors as reversers of resistance to artemisinin-based antimalarials

蛋白酶体抑制剂作为青蒿素类抗疟药耐药性的逆转剂

• 批准号: nhmrc : 1092808
• 负责人: Prof Leann Tilley
• 金额: $ 31.58万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: Development Grants
• 财政年份: 2015
• 资助国家: 澳大利亚
• 起止时间: 2015-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/proteasome-inhibitors-reversers-based-antimalarials/519393
• 关键词: Proteasome; inhibitors; reversers; resistance; artemisinin

Current antimalarial control is highly dependent on Artemisinin Combination Therapy (ACTs), which makes recent reports of decreased clinical efficacy of artemisinins extremely concerning. This project will develop proteasome inhibitors to synergise the activity of artemisinins - effectively reversing resistance. We will confirm that the selected compounds have good bioavailability, low cytotoxicity in human cell lines and efficacy in mouse models of malaria.

目前的抗疟控制高度依赖青蒿素联合治疗，这使得最近关于青蒿素临床疗效下降的报道极为令人担忧。这个项目将开发蛋白酶体抑制剂来协同青蒿素的活性——有效地逆转耐药性。我们将证实所选择的化合物具有良好的生物利用度，在人类细胞系中具有低细胞毒性，并且在小鼠疟疾模型中具有有效性。