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Updated: Mar 24, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
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Discovery and Characterization of a Novel Small-Molecule Agonist for Medium-Chain Free Fatty Acid Receptor G

Qing Zhang1, Hui Yang1, Jing Li1

  • 1Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Bio-medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China (Q.Z., X.X.); and CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China (Q.Z., H.Y., J.L., X.X.).

The Journal of Pharmacology and Experimental Therapeutics
|March 11, 2016
PubMed

Insights

Researchers identified ZQ-16, a novel and potent agonist for G protein-coupled receptor 84 (GPR84). This discovery offers a valuable tool for studying GPR84

Area of Science:

  • Pharmacology
  • Immunology
  • Molecular Biology

Background:

  • G protein-coupled receptor 84 (GPR84) is a free fatty acid receptor expressed in immune tissues.
  • GPR84 plays a role in inflammation and is a potential drug target for immune-mediated diseases.
  • Lack of specific ligands has hindered GPR84 research and drug development.

Purpose of the Study:

  • To identify potent and selective ligands for GPR84.
  • To develop tools for studying GPR84 function and potential therapeutic applications.

Main Methods:

  • Screening of 160,000 small-molecule compounds using a calcium mobilization assay.
  • Utilizing a human embryonic kidney 293 cell line stably expressing GPR84 and Gα16.
  • Characterization of identified ligands' activity on GPR84-mediated signaling pathways.

Main Results:

  • Identification of 2-(hexylthio)pyrimidine-4,6-diol (ZQ-16) as a potent and selective GPR84 agonist.
  • ZQ-16 activates multiple GPR84 signaling pathways, including calcium mobilization and ERK1/2 phosphorylation.
  • ZQ-16 demonstrates receptor desensitization, internalization, and β-arrestin interaction.

Conclusions:

  • ZQ-16 is a novel small molecule with potential as a research tool for GPR84.
  • ZQ-16 may serve as a lead compound for developing therapeutics targeting GPR84.
  • Further structural optimization of ZQ-16 could enhance its therapeutic potential.

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