Potent Small Agonists of Protease Activated Receptor 2

ACS Medicinal Chemistry Letters
Mei-Kwan YauDavid P Fairlie

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.

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Citations

Mar 5, 2016·Expert Opinion on Therapeutic Patents·Mei-Kwan YauDavid P Fairlie
Jul 6, 2016·Frontiers in Genetics·Rebecca A RoseroMenashe Bar-Eli
Feb 9, 2017·ACS Chemical Biology·Yuhong JiangDavid P Fairlie
Dec 22, 2017·The Journal of Pharmacology and Experimental Therapeutics·Yuhong JiangDavid P Fairlie
Mar 21, 2021·The FEBS Journal·Arundhasa Chandrabalan, Rithwik Ramachandran
Jul 18, 2019·ACS Medicinal Chemistry Letters·Jordan C LeSargeLeonard G Luyt
Jun 20, 2020·ACS Medicinal Chemistry Letters·Ilona KlöselPeter Gmeiner

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