Towards a cure for Malaria: Computational Design and Synthes

这个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，我们已经证实它是一个具有预防、治疗和传播阻断活性的潜在靶点。为了实现这一目标，我们将在体外和体内测试平台上合成和评估化合物，这将使学生能够针对MMV的目标候选配置文件(TCP)测试优化的PfCLK3抑制剂的性能，以促进候选开发。项目目标：1.在TCMDC-135051上进行HIT到Lead。我们以前的研究发现了一种对PfCLK3具有强烈选择性的抑制剂，即TCMDC-135051。我们计划在Hit to Lead计划中进一步开发这种抑制剂。2.筛选新的化学物质，在热门活动中发展。我们已经开发了一种PfCLK3的高通量检测方法，将用于筛选新的化合物。将在Hit to Lead计划中优化Hit to Lead计划3。测试前端运行的分子的特性，以满足MMV标准，以便随后进行候选优化。“

"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. "