广泛作为药物靶点研究的Gs偶联A2A腺苷受体(A2AAR)，已经进行了大量的临床试验。然而，目前只有一种选择性的A2AAR激动剂（雷盖诺苏，Lexiscan）和一种选择性的A2AAR拮抗剂（伊斯特地菲林，Nouriast）获得了FDA的批准，分别作为心肌灌注显像（MPI）的药理学试剂和帕金森病（PD）的联合治疗药物。腺苷广泛用于MPI中，如Adenoscan。尽管有大量的临床试验失败的情况，但基于A2AAR配体的药理活性最近加快了，特别是通过结构基药物设计。已经发现了新的类似药物的A2AAR拮抗剂，用于PD和癌症免疫治疗，并进行了许多临床试验。例如，imaradenant (AZD4635)，一种基于A2AAR的X射线结构和生物物理图谱计算设计的化合物。混合A2AAR/A2BAR拮抗剂对于癌症治疗也是有希望的。A2AAR拮抗剂还可能作为治疗阿尔茨海默病的神经保护剂具有潜力。版权所有 © 2023 Elsevier Inc. 发表。

The Gs-coupled A2A adenosine receptor (A2AAR) has been explored extensively as a pharmaceutical target, which has led to numerous clinical trials. However, only one selective A2AAR agonist (regadenoson, Lexiscan) and one selective A2AAR antagonist (istradefylline, Nouriast) have been approved by the FDA, as a pharmacological agent for myocardial perfusion imaging (MPI) and as a cotherapy for Parkinson's disease (PD), respectively. Adenosine is widely used in MPI, as Adenoscan. Despite numerous unsuccessful clinical trials, medicinal chemical activity around A2AAR ligands has accelerated recently, particularly through structure-based drug design. New drug-like A2AAR antagonists for PD and cancer immunotherapy have been identified, and many clinical trials have ensued. For example, imaradenant (AZD4635), a compound that was designed computationally, based on A2AAR X-ray structures and biophysical mapping. Mixed A2AAR/A2BAR antagonists are also hopeful for cancer treatment. A2AAR antagonists may also have potential as neuroprotective agents for treatment of Alzheimer's disease.Copyright © 2023. Published by Elsevier Inc.