Lysine-targeting covalent inhibitors

赖氨酸靶向共价抑制剂

• 批准号: 2286983
• 金额: --
• 依托单位: Institute of Cancer Research
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2286983
• 关键词: Lysine; targeting; covalent; inhibitors

The PhD student will modify high affinity reversible ligands of mutant EGFR and mutant B-Raf with lysine-targeting electrophiles using structure based rational design. The student would then characterise their inhibitors using biochemical methods to establish kinetic parameters and compare with the wild-type proteins. The inhibitors would then be applied to cancer cells to establish kinome selectivity, off-target reactivity and wild-type/mutant cell therapeutic index.

该博士生将使用基于结构的合理设计，用赖氨酸靶向亲电体修饰突变型EGFR和突变型B-Raf的高亲和力可逆配体。然后，学生将使用生物化学方法对他们的抑制剂进行分析，以建立动力学参数，并与野生型蛋白质进行比较。然后将抑制剂应用于癌细胞以建立激酶组选择性、脱靶反应性和野生型/突变细胞治疗指数。