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Identifying 2PHDO as a SOCE Inhibitor from Chinese Herbal Extracts

Jindou Liu¹, Hao Deng^2,3,4, Yaxin Li¹

¹Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.

Current Pharmaceutical Biotechnology

|June 15, 2023

Summary

Researchers discovered 2PHDO, a novel inhibitor of store-operated calcium entry (SOCE), from Chinese herbal medicine. This compound effectively blocks SOCE and may serve as a template for new therapeutics targeting SOCE-related diseases.

Keywords:

SOCE STIM1 Orai1 inhibitor Chinese herbal medicine 2PHDO

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Area of Science:

Biochemistry
Pharmacology
Immunology

Background:

Store-operated calcium entry (SOCE) is vital for immune, muscle, and neuronal functions.
Developing specific SOCE inhibitors is crucial for treating related disorders but remains challenging.

Purpose of the Study:

To identify novel SOCE inhibitors from Chinese herbal extracts.
To investigate the mechanism of action of a newly identified inhibitor.

Main Methods:

Screening of Chinese herbal extracts for SOCE inhibitory activity.
Characterization of inhibitor potency, specificity, and mechanism using cellular assays.
Investigated STIM1 and Orai1 interactions.

Main Results:

Identified 2PHDO, a novel SOCE inhibitor, from herbal extracts.
2PHDO inhibits SOCE and NFAT translocation in various cell types with IC50 around 1 µM.
2PHDO specifically targets Orai1, without affecting STIM1 activation or STIM1-Orai1 coupling.

Conclusions:

2PHDO is a potent and specific SOCE inhibitor.
2PHDO can serve as a lead compound for developing new drugs for SOCE-related diseases.
Screening herbal medicine is a feasible strategy for discovering novel SOCE inhibitors.