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PfCLK 3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，并且已经被我们验证为具有提供预防、治疗和传递阻断活性的潜力的靶标。为了实现这一目标，我们将在体外和体内试验平台上合成和评估化合物，这将使学生能够测试优化的PfCLK 3抑制剂对MMV的目标候选人特征（TCP）的特性，以用于先导候选人开发的化合物。项目目标：1.在TCMDC-135051上进行命中。我们以前的研究发现了一种有效的和选择性的PfCLK 3抑制剂，即TCMDC-135051。我们计划在一个打击铅计划中进一步开发这种抑制剂。2.筛选新的化学物质，并在一个打击领先的运动发展。我们已经开发了一种用于PfCLK 3的高通量测定，该测定将用于筛选新化合物。点击将在一个点击中进行优化，以引导程序3。测试前运行分子的特性，以满足后续Lead to Candidate优化的MMV标准。"

"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. "