Towards a cure for Malaria: Computational Design and Synthes

“该项目旨在开发一种针对疟疾蛋白激酶PfCLK3的早期铅抑制剂。这种蛋白激酶在RNA剪接中起着至关重要的作用，并且已经被我们证实是具有预防、治疗和传输阻断活性的潜在靶标。为了实现这一目标，我们将在体外和体内的分析平台上合成和评估化合物，这将允许学生测试优化的PfCLK3抑制剂针对MMV的目标候选谱（tcp）的特性，用于先导到候选化合物的开发。项目目标：1；对TCMDC-135051进行打击。我们之前的研究发现了一种有效的选择性PfCLK3抑制剂，即TCMDC-135051。我们计划在hit to lead项目中进一步开发这种抑制剂。2. 筛选新的化学物质，并开发一个打击，以带动运动。我们已经开发了一种高通量的PfCLK3检测方法，将用于筛选新化合物。热门歌曲将在热门歌曲中进行优化，以引导第三期节目。测试前端运行分子的性能，以满足MMV标准，然后进行候选优化。”

"This project aims to develop an Early Lead inhibitor against the malaria protein kinase PfCLK3. This protein kinase plays an essential role in RNA splicing and has been validated by us to be a target with the potential to offer prophylactic, curative and transmission blocking activity. To deliver on this aim we will synthesise and assess compounds in vitro and in vivo assay platforms what will allow the student to test the properties of optimised PfCLK3 inhibitors against MMV's Target Candidate Profiles (TCPs) for compounds for Lead to Candidate development. The project objectives: 1. Conduct hit to lead on TCMDC-135051. Our previous studies discovered a potent and selective inhibitor to PfCLK3, namely TCMDC-135051. We plan to further develop this inhibitor in a hit to lead programme. 2. Screen for novel chemical matter and develop in a hit to lead campaign. We have developed a high throughput assay for PfCLK3 that will be used to screen new compounds. Hits will be optimised in a hit to lead programme 3. Test front running molecules for properties that meet MMV criteria for subsequent Lead to Candidate optimisation. "