Williams M
Neuroscience Discovery, Abbott Laboratories, Abbott Park, IL 60064, USA.
Ciba Found Symp. 1996;198:309-21. doi: 10.1002/9780470514900.ch18.
Advances in the molecular cloning, expression and functional characterization of the P2 purinoceptor superfamily have provided a wealth of data to support a diverse functional role for ATP and related nucleotides in the regulation of tissue function. As with other receptor superfamilies, it is likely that distinct subtypes of each receptor will subserve discrete functions depending on tissue distribution and disease pathophysiology. At the present time, ATP is being evaluated as an anticancer agent and as an anaesthesia adjunct whereas UTP is studied as a novel treatment for cystic fibrosis. ARL67085 is a potent and selective P2T receptor antagonist that has potential as a novel antithrombotic agent. The key to exploiting the P2 purinoceptor area to enhance understanding of disease aetiology and concurrent therapeutic potential will be to focus efforts on the identification of novel pharmacophores that have potent and selective interactions with the various receptor subtypes as potential new leads. To this end, the use of high-throughput screening in conjunction with combinatorial chemical, conventional chemical and natural product library compound sources will be critical.
P2嘌呤受体超家族在分子克隆、表达及功能特性方面的进展，已提供了大量数据，以支持ATP及相关核苷酸在调节组织功能中具有多种功能作用。与其他受体超家族一样，每种受体的不同亚型可能会根据组织分布和疾病病理生理学发挥不同的功能。目前，ATP正在作为一种抗癌剂和麻醉辅助剂进行评估，而UTP则作为囊性纤维化的一种新疗法进行研究。ARL67085是一种强效且选择性的P2T受体拮抗剂，具有作为新型抗血栓形成剂的潜力。利用P2嘌呤受体领域来增进对疾病病因的理解以及并发治疗潜力的关键，将是集中精力鉴定与各种受体亚型具有强效且选择性相互作用的新型药效基团，作为潜在的新先导物。为此，结合组合化学、传统化学和天然产物库化合物来源进行高通量筛选将至关重要。
