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Potent Small Agonists of Protease Activated Receptor 2.

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.

SUBMITTER: Yau MK

PROVIDER: S-EPMC4716605 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Potent Small Agonists of Protease Activated Receptor 2.

Yau Mei-Kwan MK Suen Jacky Y JY Xu Weijun W Lim Junxian J Liu Ligong L Adams Mark N MN He Yaowu Y Hooper John D JD Reid Robert C RC Fairlie David P DP

ACS medicinal chemistry letters 20151130 1

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 ...[more]

PMID: 26819675

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