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

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。这种情况有70-90%的死亡率，是英国和巴西的主要公共卫生问题。在巴西，脓毒症相关死亡人数急剧增加（2002年为9.8%，2010年为16.5%）。脓毒症引起的心血管衰竭治疗的一个主要挑战是标准的血管加压药和正性肌力药治疗无效。在由于社会经济或地理原因而不易获得医疗保健的人群中，这种情况会加剧，导致潜在感染的恶化。拟议的工作旨在利用最近的知识，药物的能力，以偏见的反应，从细胞表面受体特定的细胞内信号传导途径，以开发在败血症有效的正性肌力和血管加压治疗。

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.