From Fragment-screening to Fragment-growing - new strategies for drug discovery

从片段筛选到片段生长——药物发现的新策略

• 批准号: 2449008
• 金额: --
• 依托单位: Durham University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2449008
• 关键词: Fragment; screening; growing; new; strategies

Type-2 diabetes represents a major and growing health problem in particular in industrialised countries. Although many cases may be preventable by life-style changes and better diet, numbers are steadily rising. Human Glucose Kinase (GK) has been identified as one potential target for intervention but so far, no drug targeting this protein has entered the market. In this project we will employ and develop fragment-based methods to identify new lead compounds binding to GK. Over the last decade, fragment-based methods have made a major impact on drug discovery in academia and pharmaceutical research. Recent advances in high-throughput structure determination and the development of targeted fragment libraries were instrumental, however, one of the remaining bottlenecks is the translation from multiple fragment binding sites into a credible lead compound. The overall goal of the proposed project is to identify new chemical entities that act as allosteric activators of human GK and present lead candidates for future drug development using a new fragment-based drug discovery approach. These efforts will be supported with the expertise from CCDC to develop new algorithms to support fragment-linking and growing approach.

2型糖尿病是一个重大且日益严重的健康问题，特别是在工业化国家。尽管许多病例可能可以通过生活方式的改变和更好的饮食来预防，但这一数字正在稳步上升。人葡萄糖激酶(GK)已被确定为一个潜在的干预靶点，但到目前为止，还没有针对该蛋白的药物进入市场。在这个项目中，我们将使用和开发基于片段的方法来识别与GK结合的新的先导化合物。在过去的十年里，基于片段的方法对学术界和药物研究中的药物发现产生了重大影响。最近在高通量结构测定和靶向片段文库开发方面的进展是有益的，然而，仍然存在的瓶颈之一是从多个片段结合位点到可信的先导化合物的翻译。拟议项目的总体目标是确定作为人类GK变构激活剂的新化学实体，并提出使用基于片段的新药物发现方法进行未来药物开发的主要候选对象。这些努力将得到CCDC的专业知识的支持，以开发新的算法来支持片段链接和增长方法。