@article{APS5129,
author = {Jian-hua Yan and Qun-yi Li and Jean A Boutin and M Pierre Renard and Yi-xiang Ding and Xiao-jiang Hao and Wei-min Zhao and Ming-wei Wang},
title = {High-throughput screening of novel antagonists on melanin-concentrating hormone receptor-1},
journal = {Acta Pharmacologica Sinica},
volume = {29},
number = {6},
year = {2016},
keywords = {},
abstract = {Aim: To find new antagonists on human melanin-concentrating hormone receptor-1 (MCHR-1) through high-throughput screening (HTS) of a diverse compound library.
Methods: MCHR-1, [3H]SNAP7941, and FlashBlue G-protein-coupled receptor beads were used to measure the receptor-binding activities of various compounds based on scintillation proximity assay (SPA) technology. The guanosine 5′ (γ-[35S]thio) triphosphate ([35S]GTPγS) binding assay was subsequently applied to functionally characterize the “hits” identified by the HTS campaign.
Results: Of the 48 240 compounds screened with the SPA method, 12 hits were confirmed to possess MCHR-1 binding activities, 8 were functionally studied subsequently with the [35S]GTPγS binding assay, and only 1 compound (NC127816) displayed moderate human MCHR-1 binding affinity (Ki=115.7 nmol/L) and relatively potent antagonism (KB=23.8 nmol/L). This compound shares a novel scaffold (1-ethoxy-2H-2-aza-1-phospha-naphthalene 1-oxide) with 3 other analogs in the group.
Conclusion: Considering the marked difference in molecular shape and electrostatic status between NC127816 and the structures reported elsewhere, we anticipate that its derivatives may represent a new class of potent MCHR-1 modulators.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/5129}
}