Pharmaceutical & Medicinal Chemistry, PharmaCenter Bonn, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Methods Mol Biol. 2022;2510:31-52. doi: 10.1007/978-1-0716-2384-8_2.
The P2X7 receptor has been proposed as a novel drug target for different types of diseases associated with inflammation, including brain diseases, peripheral inflammation, and cancers. Structurally diverse P2X7 receptor antagonists, mainly negative allosteric modulators (NAMs), have been developed in recent years, and several P2X7 receptor antagonists are currently evaluated in clinical trials. The P2X7 receptor requires high micro- to even millimolar ATP concentrations to be activated. Selective agonists for the P2X7 receptor are not available. Positive allosteric modulators (PAMs) have been described, but PAMs with high potency and selectivity are still lacking. This chapter discusses medicinal chemistry approaches toward the development of P2X7 receptor modulators and presents a selection of recommended tool compounds for studying P2X7 receptors in humans and rodents.
P2X7 受体已被提议作为与炎症相关的不同类型疾病（包括脑部疾病、外周炎症和癌症）的新型药物靶点。近年来，已经开发出结构多样的 P2X7 受体拮抗剂，主要是负变构调节剂（NAM），目前有几种 P2X7 受体拮抗剂正在临床试验中进行评估。P2X7 受体需要高至毫微微摩尔甚至毫摩尔浓度的 ATP 才能被激活。目前还没有针对 P2X7 受体的选择性激动剂。已经描述了正变构调节剂（PAM），但仍缺乏高活性和选择性的 PAM。本章讨论了开发 P2X7 受体调节剂的药物化学方法，并介绍了一些用于研究人和啮齿动物 P2X7 受体的推荐工具化合物。
