Functional assays to define agonists and antagonists of the sigma-2 receptor

Analytical Biochemistry
Chenbo ZengRobert H Mach

Abstract

The sigma-2 receptor has been identified as a biomarker in proliferating tumors. To date there is no well-established functional assay for defining sigma-2 agonists and antagonists. Many sigma-2 ligands with diverse structures have been shown to induce cell death in a variety of cancer cells by triggering caspase-dependent and independent apoptosis. Therefore, in the current study, we used the cell viability assay and the caspase-3 activity assay to determine sigma-2 agonists and antagonists. Three classes of sigma-2 ligands developed in our laboratory were evaluated for their potency to induce cell death in two tumor cell lines, mouse breast cancer cell line EMT-6 and human melanoma cell line MDA-MB-435. The data showed that the EC50 values of the sigma-2 ligands using the cell viability assay ranged from 11.4μM to >200μM, which were comparable with the EC50 values obtained using the caspase-3 assay. Based on the cytotoxicity of a sigma-2 ligand relative to that of siramesine, a commonly accepted sigma-2 agonist, we have categorized our sigma-2 ligands into agonists, partial agonists, and antagonists. The establishment of functional assays for defining sigma-2 agonists and antagonists will facilitate functional characterizatio...Continue Reading

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Citations

Nov 18, 2015·The Journal of Pharmacology and Experimental Therapeutics·Hilary NicholsonWayne D Bowen
Dec 26, 2015·Nuclear Medicine and Biology·Mehran MakvandiDaniel A Pryma
Oct 11, 2015·Biochemical and Biophysical Research Communications·Mehran MakvandiRobert H Mach
May 18, 2016·The Journal of Pharmacology and Experimental Therapeutics·Jonathan L KatzChristopher R McCurdy
Jul 13, 2016·Future Medicinal Chemistry·Martín EstradaMaría Isabel Rodríguez-Franco
Jan 5, 2017·Expert Opinion on Therapeutic Patents·Simona CollinaAnna Tesei
Jun 24, 2017·ACS Chemical Neuroscience·James J SahnTheodore J Price
Jun 3, 2015·The Journal of Pharmacology and Experimental Therapeutics·Hilary NicholsonWayne D Bowen
Aug 5, 2020·Expert Opinion on Therapeutic Targets·James Michael BrimsonTewin Tencomnao
Nov 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kai YangTaolei Sun
Oct 14, 2020·European Journal of Medicinal Chemistry·Xiao-Yang XieYun-Sheng Huang
Oct 3, 2020·Bioorganic & Medicinal Chemistry·Benjamin SchinorGünter Haufe
Mar 30, 2017·Biochemical and Biophysical Research Communications·Elizabeth S McDonaldChenbo Zeng
Jun 3, 2021·Journal of Medicinal Chemistry·Antonino N FallicaSebastiano Intagliata
Jun 3, 2021·International Journal of Molecular Sciences·Rareş-Petru MoldovanWinnie Deuther-Conrad
Apr 25, 2017·ACS Medicinal Chemistry Letters·James J SahnStephen F Martin

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