Towards a cure for Malaria: Computational Design and Synthes

治愈疟疾：计算设计和合成

• 批准号: 2607115
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2607115
• 关键词: Towards; cure; Malaria; Computational; Design

"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. "

“该项目旨在开发一种针对疟疾蛋白激酶 PfCLK3 的早期先导抑制剂。这种蛋白激酶在 RNA 剪接中发挥着重要作用，并已被我们验证为具有提供预防、治疗和传播阻断活性潜力的靶点。为了实现这一目标，我们将在体外和体内分析平台上合成和评估化合物，这将使学生能够根据 MMV 的目标候选谱 (TCP) 测试优化的 PfCLK3 抑制剂的特性，以了解铅的化合物项目目标： 1. TCMDC-135051 的先导作用 我们之前的研究发现了一种有效的、选择性的 PfCLK3 抑制剂，即 TCMDC-135051，我们计划在先导作用计划中进一步开发这种抑制剂。筛选新化学物质并在先导化合物中进行开发 我们开发了一种 PfCLK3 的高通量测定方法，该方法将用于筛选新化合物。程序 3. 测试前端运行分子的特性是否满足 MMV 标准，以便随后进行候选优化。 ”