P2Y Receptors in Health and Disease
P2Y Receptors in Health and Disease
复制标题
DOI：
10.1016/b978-0-12-385526-8.00013-8
复制
发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Erlinge, David
中科院分区：
文献类型：
--
作者：
Erlinge, David
嘌呤和嘧啶敏感的P2Y受体属于G蛋白偶联受体的大组，其是当今临床上使用的约三分之一的药物的靶标。因此，P2Y受体可能是药物开发的有用靶点并不意外。本章将讨论基于P2Y受体的治疗目前使用的，在开发和可能的未来发展。血小板抑制剂阻断ADP受体P2Y（12）减少心肌梗死，中风和心血管疾病患者的死亡率。氯吡格雷（Plavidogrel）多年来一直是世界上第二大畅销药物。改良的P2Y（12）抑制剂普拉格雷（prasugrel）、替格瑞洛（ticagrelor）和依林格雷（elinogrel）现在进入临床，具有更显著的保护作用。囊性纤维化是一种单基因疾病，其中氯离子分泌减少导致严重的肺部疾病和早期死亡。P2Y（2）受体激动剂Denufosol已被证明可以改善肺功能，并有望很快被引入囊性纤维化的治疗。在临床前研究中，有迹象表明P2Y受体对糖尿病、骨质疏松症、心血管和动脉粥样硬化疾病很重要。总之，P2Y受体对许多疾病的人类健康很重要，我们可以期待未来更有益的靶向P2Y受体的药物。
The purine- and pyrimidine-sensitive P2Y receptors belong to the large group of G-protein-coupled receptors that are the target of approximately one-third of the pharmaceutical drugs used in the clinic today. It is therefore not unexpected that the P2Y receptors could be useful targets for drug development. This chapter will discuss P2Y receptor-based therapies currently used, in development and possible future developments.The platelet inhibitors blocking the ADP-receptor P2Y(12) reduce myocardial infarction, stroke, and mortality in patients with cardiovascular disease. Clopidogrel (Plavix) was for many years the second most selling drug in the world. The improved P2Y(12) inhibitors prasugrel, ticagrelor, and elinogrel are now entering the clinic with even more pronounced protective effects.The UTP-activated P2Y(2) receptor stimulates ciliary movement and secretion from epithelial cells. Cystic fibrosis is a monogenetic disease where reduced chloride ion secretion results in a severe lung disease and early death. No specific treatment has been available, but the P2Y(2) agonist Denufosol has been shown to improve lung function and is expected to be introduced as treatment for cystic fibrosis soon.In preclinical studies, there are indications that P2Y receptors can be important for diabetes, osteoporosis, cardiovascular, and atherosclerotic disease. In conclusion, P2Y receptors are important for the health of humans for many diseases, and we can expect even more beneficial drugs targeting P2Y receptors in the future.