McCoy Joshua G, Marugan Juan J, Liu Ke, Zheng Wei, Southall Noel, Huang Wenwei, Heilig Markus, Austin Christopher P
NIH Chemical Genomic Center, National Human Genome Research Institute, National Institutes of Heath, 9800 Medical Center Drive, Rockville, 20850, MD, USA.
ACS Chem Neurosci. 2010 Aug 18;1(8):559-574. doi: 10.1021/cn100040h.
Antagonists of the Neuropeptide S Receptor have been postulated as promising therapeutics in the treatment of respiratory, sleep, anxiety, and addictive disorders. Here we present the SAR of a new series of orthosteric antagonists. Neuropeptide S Receptor signaling is coupled to both Gq and Gs proteins, and we observe that different analogues in this structural series can selectively antagonize these two pathways. Many G-protein coupled receptors transduce signals through multiple pathways. Selective antagonism of these pathways may lead the way to the development of more targeted pharmacological profiles and therapies.
神经肽S受体拮抗剂已被认为是治疗呼吸、睡眠、焦虑和成瘾性疾病的有前景的疗法。在此，我们展示了一系列新型正构拮抗剂的构效关系。神经肽S受体信号传导与Gq和Gs蛋白均偶联，并且我们观察到该结构系列中的不同类似物可选择性拮抗这两条途径。许多G蛋白偶联受体通过多种途径转导信号。对这些途径的选择性拮抗可能为开发更具针对性的药理学特征和疗法铺平道路。
