Targeting Cytotoxic Agents to Tumours through Small Molecule Covalent Binding

通过小分子共价结合将细胞毒性药物靶向肿瘤

• 批准号: 1770103
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1770103
• 关键词: Targeting; Cytotoxic; Agents; Tumours; through

OverviewAbstractThe ability to target a potent cytotoxic agent selectively to a tumour is very attractive and has been a holy grail of cancer research for many years. We are developing methods that use covalent inhibitors as targeting agents to carry drug molecules to tumour cells. Once this occurs, a subsequent reaction will trigger release of a linked cytotoxic agent. Provided the protein target of the covalent inhibitor is overexpressed in tumour cell, the cytotoxic agent will be able to target these cells selectively. We anticipate that this will lead to improved cancer cell killing with the potential for reduced side effects.In the project we will develop new release mechanisms, optimize these mechanisms using model systems and then assess the potential of the systems to exert selective anti-tumour effects in cellular experiments. These results will then be applied to the development a range of systems using different cytotoxic effects and targeting vehicles.ImpactThis work will explore a new method of selective delivery of molecules to tumour cells. We anticipate that insights gained from this will lead to new approaches to cancer therapy with potential advantages over existing protocols. The general principle will also be applicable to specific targeting of proteins in other disease areas and in chemical biology applications.

将一种有效的细胞毒剂选择性地靶向肿瘤的能力是非常有吸引力的，多年来一直是癌症研究的圣杯。我们正在开发使用共价抑制剂作为靶向剂的方法，以携带药物分子到肿瘤细胞。一旦发生这种情况，随后的反应将触发连接的细胞毒剂的释放。如果共价抑制物的蛋白靶点在肿瘤细胞中过表达，细胞毒剂将能够选择性地靶向这些细胞。在该项目中，我们将开发新的释放机制，使用模型系统优化这些机制，然后评估这些系统在细胞实验中发挥选择性抗肿瘤作用的潜力。这些结果将被应用于开发一系列使用不同细胞毒性效应和靶向载体的系统。这项工作将探索一种选择性地将分子输送到肿瘤细胞的新方法。我们预计，由此获得的洞察力将导致新的癌症治疗方法，其潜在优势超过现有方案。一般原则也将适用于在其他疾病领域和在化学生物学应用中对蛋白质的特定靶向。