Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands (A.P.IJ.); National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Molecular Recognition Section, Bethesda, Maryland (K.A.J.); Universität Bonn, Bonn, Germany (C.E.M.); New York University School of Medicine, New York, New York (B.N.C.); and Center for Neurosciences and Cell Biology and Faculty of Medicine, University of Coimbra, Coimbra, Portugal (R.A.C.)
Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands (A.P.IJ.); National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Molecular Recognition Section, Bethesda, Maryland (K.A.J.); Universität Bonn, Bonn, Germany (C.E.M.); New York University School of Medicine, New York, New York (B.N.C.); and Center for Neurosciences and Cell Biology and Faculty of Medicine, University of Coimbra, Coimbra, Portugal (R.A.C.).
Pharmacol Rev. 2022 Apr;74(2):340-372. doi: 10.1124/pharmrev.121.000445.
Our previous International Union of Basic and Clinical Pharmacology report on the nomenclature and classification of adenosine receptors (2011) contained a number of emerging developments with respect to this G protein-coupled receptor subfamily, including protein structure, protein oligomerization, protein diversity, and allosteric modulation by small molecules. Since then, a wealth of new data and results has been added, allowing us to explore novel concepts such as target binding kinetics and biased signaling of adenosine receptors, to examine a multitude of receptor structures and novel ligands, to gauge new pharmacology, and to evaluate clinical trials with adenosine receptor ligands. This review should therefore be considered a further update of our previous reports from 2001 and 2011. SIGNIFICANCE STATEMENT: Adenosine receptors (ARs) are of continuing interest for future treatment of chronic and acute disease conditions, including inflammatory diseases, neurodegenerative afflictions, and cancer. The design of AR agonists ("biased" or not) and antagonists is largely structure based now, thanks to the tremendous progress in AR structural biology. The A- and AAR appear to modulate the immune response in tumor biology. Many clinical trials for this indication are ongoing, whereas an AAR antagonist (istradefylline) has been approved as an anti-Parkinson agent.
我们之前的国际基础和临床药理学协会关于腺苷受体命名和分类的报告（2011 年）包含了这一家族中一些新兴的发展，包括蛋白结构、蛋白寡聚化、蛋白多样性和小分子的变构调节。自那时以来，已经增加了大量的新数据和结果，使我们能够探索新的概念，如靶结合动力学和腺苷受体的偏向信号转导，检查大量的受体结构和新型配体，评估新的药理学，并评估与腺苷受体配体的临床试验。因此，本综述应被视为对我们之前 2001 年和 2011 年报告的进一步更新。
腺苷受体（ARs）对于慢性和急性疾病状况的未来治疗仍然具有重要意义，包括炎症性疾病、神经退行性疾病和癌症。由于 AR 结构生物学的巨大进展，AR 激动剂（“偏向”或非偏向）和拮抗剂的设计在很大程度上是基于结构的。A 型和 A2AAR 似乎在肿瘤生物学中调节免疫反应。许多针对这一适应症的临床试验正在进行，而 A2AAR 拮抗剂（伊曲茶碱）已被批准为抗帕金森药物。
