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Discovery and validation of novel protein lipidation drug targets in cancer

癌症中新型蛋白质脂化药物靶点的发现和验证

基本信息

批准号：
2755949
负责人：
金额：
--
依托单位：
Imperial College London
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-2755949
关键词：
Discovery validation novel protein lipidation

项目摘要

Lipidation is a rich and widespread class of protein post-translational modification (PTM), with key roles in signalling, cell death, immunity, protein stability and trafficking. More than 150 oncoproteins and potential cancer drug targets are lipidated, including many not amenable to traditional drug discovery. Intervening in the extensive network of enzymes regulating protein lipidation presents a unique opportunity to target these 'undruggable' proteins, an approach recently validated with the first FDA approval of a lipid transferase inhibitor in 2020. We have developed chemical proteomic technologies to study all the major classes of protein lipidation and delivered target validation and novel lipidation inhibitors into preclinical development for oncology, founding Myricx Pharma in 2019 to translate our findings into first in class therapeutics to benefit cancer patients. In this project, in collaboration with scientists at the Francis Crick Institute, Institute of Cancer Research (ICR) and in industry working on development of lipidation inhibitors in cancer, we will apply chemical probe design, chemical genetics, proteomics, and mechanistic drug target validation using modern gene editing and screening approaches to identify and validate novel targets for cancer therapy.

脂质化是一种丰富而广泛的蛋白质翻译后修饰（PTM），在信号传导、细胞死亡、免疫、蛋白质稳定性和运输中发挥关键作用。超过150种癌蛋白和潜在的癌症药物靶标被脂化，包括许多不适合传统药物发现的蛋白。干预调节蛋白质脂化的广泛酶网络提供了一个独特的机会来靶向这些“不可药物化”的蛋白质，这一方法最近在2020年首次获得FDA批准的脂质转移酶抑制剂中得到了验证。我们开发了化学蛋白质组学技术来研究所有主要类别的蛋白质脂化，并将靶标验证和新型脂化抑制剂用于肿瘤学的临床前开发，于2019年成立了Myricx Pharma，将我们的发现转化为一流的治疗方法，使癌症患者受益。在这个项目中，与弗朗西斯克里克研究所，癌症研究所（ICR）的科学家合作，并在癌症中开发脂化抑制剂的行业中，我们将应用化学探针设计，化学遗传学，蛋白质组学和机械药物靶标验证，使用现代基因编辑和筛选方法来识别和验证癌症治疗的新靶标。