Identification and development of compounds targeting childhood brain cancer

针对儿童脑癌的化合物的鉴定和开发

• 批准号: 2751147
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2751147
• 关键词: Identification; development; compounds; targeting; childhood

Our collaborators have identified a protein called ATIC, an enzyme that catalyses that last two steps of the de novo purine biosynthesis pathway, as being important for the survival of a subset of childhood brain tumours. Their experiments with a small molecule ATIC inhibitor developed by our lab has shown that these tumour cell lines are sensitive to ATIC inhibition, significantly increasing the survival rate in pre-clinical mouse models. In this project, we will develop next-generation inhibitors of ATIC with improved in vitro and cell-based activity. This will involve synthesis and testing of analogues of our ATIC inhibiotr. In addition to the medicinal chemistry core of this project, the project will proivide training in a variety of chemical biology teniques such as recombinant protein-expression and purificaiton, and biochemical and cell-based assays.

我们的合作者已经确定了一种名为ATIC的蛋白质，这是一种催化从头嘌呤生物合成途径的最后两个步骤的酶，对于儿童脑肿瘤的生存至关重要。他们用我们实验室开发的小分子ATIC抑制剂进行的实验表明，这些肿瘤细胞系对ATIC抑制敏感，显著提高了临床前小鼠模型的存活率。在这个项目中，我们将开发下一代ATIC抑制剂，其具有改进的体外和细胞活性。这将涉及我们的ATIC抑制剂类似物的合成和测试。除了该项目的药物化学核心外，该项目还将提供各种化学生物学技术的培训，如重组蛋白表达和纯化，以及生物化学和基于细胞的测定。