蛋白酶激活受体2的强效小分子激动剂。
Potent Small Agonists of Protease Activated Receptor 2.
作者信息
Yau Mei-Kwan, Suen Jacky Y, Xu Weijun, Lim Junxian, Liu Ligong, Adams Mark N, He Yaowu, Hooper John D, Reid Robert C, Fairlie David P
机构信息
Institute for Molecular Bioscience, The University of Queensland , Brisbane, Qld 4072, Australia.
Translational Research Institute, Mater Research Institute, The University of Queensland , Woolloongabba, Qld 4102, Australia.
出版信息
ACS Med Chem Lett. 2015 Nov 30;7(1):105-10. doi: 10.1021/acsmedchemlett.5b00429. eCollection 2016 Jan 14.
Abstract
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 (EC50 = 15-100 nM, iCa(2+), 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.
摘要
许多蛋白酶切割PAR2的N端，导致构象变化从而激活细胞。与PAR2新暴露的N端序列相对应的合成肽在微摩尔浓度下也能激活该受体。本文报道的PAR2选择性小分子在纳摩尔浓度下（EC50 = 15 - 100 nM，细胞内钙离子，CHO - hPAR2细胞）可诱导PAR2介导的细胞内钙信号传导。这些是激活PAR2介导的钙释放和趋化作用最有效且高效的小分子配体，包括对人乳腺癌和前列腺癌细胞。
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