PDF(Pubmed)
Abstract：
Although drugs targeting the orthosteric binding site of cannabinoid receptors (CBRs) have several therapeutic effects on human physiological and pathological conditions, they can also cause serious adverse effects. Only a few orthosteric ligands have successfully passed clinical trials. Recently, allosteric modulation has become a novel option for drug discovery, with fewer adverse effects and the potential to avoid drug overdose. In this review, we highlight novel findings related to the drug discovery of allosteric modulators (AMs) targeting CBRs. We summarize newly synthesized AMs and the reported/predicted allosteric binding sites. We also discuss the structural determinants of the AMs binding as well as the molecular mechanism of CBR allostery.
摘要：
尽管靶向大麻素受体（CBRs）的正构结合位点的药物对人体生理和病理状况具有多种治疗作用，它们也会造成严重的不良影响。只有少数正构配体已成功通过临床试验。最近,变构调制已成为药物发现的新选择，副作用更少，并且有可能避免药物过量。在这次审查中,我们重点介绍了与针对CBR的变构调节剂（AMs）的药物发现相关的新发现。我们总结了新合成的AM和报道/预测的变构结合位点。我们还讨论了AMs结合的结构决定因素以及CBR变构的分子机理。
