Potent Small Agonists of Protease Activated Receptor 2

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• 作者：Mei-Kwan Yau ; Jacky Y. Suen ; Weijun Xu ; Junxian Lim ; Ligong Liu ; Mark N. Adams ; Yaowu He ; John D. Hooper ; Robert C. Reid ; David P. Fairlie
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：January 14, 2016
• 年：2016
• 卷：7
• 期：1
• 页码：105-110
• 全文大小：359K
• ISSN：1948-5875

文摘

Many proteases cut the PAR2 N-terminus resulting in conformational changes that activate cells. Synthetic peptides corresponding to newly exposed N-terminal sequences of PAR2 also activate the receptor at micromolar concentrations. PAR2-selective small molecules reported here induce PAR2-mediated intracellular calcium signaling at nanomolar concentrations (EC<sub>50sub> = 15–100 nM, iCa<sup>2+sup>, CHO-hPAR2 cells). These are the most potent and efficient small molecule ligands to activate PAR2-mediated calcium release and chemotaxis, including for human breast and prostate cancer cells.