Repurposing Registered Drugs as Antagonists for Protease-Activated Receptor 2
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- 作者：Weijun Xu ; Junxian Lim ; Chai-Yeen Goh ; Jacky Y. Suen ; Yuhong Jiang ; Mei-Kwan Yau ; Kai-Chen Wu ; Ligong Liu ; David P. Fairlie
- 刊名：Journal of Chemical Information and Modeling
- 出版年：2015
- 出版时间：October 26, 2015
- 年：2015
- 卷：55
- 期：10
- 页码：2079-2084
- 全文大小：358K
- ISSN：1549-960X
文摘
Virtual screening of a drug database identified Carvedilol, Loratadine, Nefazodone and Astemizole as PAR2 antagonists, after ligand docking and molecular dynamics simulations using a PAR2 homology model and a putative binding mode of a known PAR2 ligand. The drugs demonstrated competitive binding and antagonism of calcium mobilization and ERK1/2 phosphorylation in CHO-hPAR2 transfected cells, while inhibiting IL-6 secretion in PAR2 expressing MDA-MB-231 breast cancer cells. This research highlights opportunities for GPCR hit-finding from FDA-approved drugs.