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ID: ALA2413074

Journal: Eur J Med Chem

Title: Structure-based drug design using GPCR homology modeling: toward the discovery of novel selective CysLT2 antagonists.

Authors: Dong X, Zhao Y, Huang X, Lin K, Chen J, Wei E, Liu T, Hu Y.

Abstract: 3D structure of CysLT2 receptor was constructed by using homology modeling and molecular simulations. The binding pocket of CysLT2 receptor and the proposition of the interaction mode between CysLT2 and HAMI3379 were identified. A series of dicarboxylated chalcones was then virtually evaluated through molecular docking studies. A total of six compounds 13a-f with preferable scores was further synthesized and tested for CysLT2 antagonistic activities by determination of the cytosolic free Ca(2+) levels in HEK293 cells. Compounds 13e and 13f exhibited potent and selective CysLT2 antagonistic activities with IC50 values being 7.5 and 0.25 μM, respectively.

CiteXplore: 23455026

DOI: 10.1016/j.ejmech.2013.01.041