Newton 001 Development of new GPCRs interacting drugs to treat inflammatory diseases

Newton 001 开发新的 GPCR 相互作用药物来治疗炎症性疾病

• 批准号: MR/M026205/1
• 负责人: Stephen Hill
• 金额: $ 6.2万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM026205%2F1
• 关键词: Newton; 001; Development; new; GPCRs

The overwhelming systemic inflammatory response triggered by acute infection (sepsis) and its progression into septic shock can lead to progressive organ dysfunction. This condition has a 70-90% mortality rate and is a major public health problem both the UK and Brazil. In Brazil there has been a dramatic increase in the number of sepsis-associated deaths (9.8% in 2002 to 16.5% in 2010). A major challenge in the treatment of sepsis-induced cardiovascular collapse is the fact thatit is not responsive to standard vasopressor and inotropic treatments. This situation is aggravated in populations where healthcare provision is not readily accessible, either for socio-economical or geographical reasons, leading to exacerbation of the underlying infection. The proposed work intends to exploit recent knowledge of the ability of drugs to bias responses from cell surface receptors to particular intracellular signalling pathways in order to develop inotropic and vasopressor treatments that are effective in sepsis.

急性感染（脓毒症）引发的压倒性全身炎症反应及其进展为脓毒性休克可导致进行性器官功能障碍。这种情况的死亡率为 70-90%，是英国和巴西的一个主要公共卫生问题。在巴西，败血症相关死亡人数急剧增加（2002 年为 9.8%，2010 年为 16.5%）。治疗脓毒症引起的心血管衰竭的一个主要挑战是它对标准血管加压药和正性肌力治疗没有反应。在由于社会经济或地理原因而不易获得医疗保健服务的人群中，这种情况会更加严重，从而导致潜在感染的加剧。拟议的工作旨在利用药物将细胞表面受体的反应偏向特定细胞内信号通路的能力的最新知识，以开发对脓毒症有效的正性肌力和血管加压药治疗方法。