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<p>Disturbances in calcium signaling and, in particular, store-operated calcium entry are associated with a wide range of diseases, including neurodegenerative, oncological, and autoimmune pathologies. Inhibitors of store-operated calcium entry have a neuroprotective effect and suppress metastasis, which makes store-operated channels an attractive target for drug design. Previously, we showed that 1,2,3,4-dithiadiazole derivatives are negative modulators of store-operated calcium channels that are normally activated by STIM1 and STIM2 proteins. Here, we studied the specificity of action of one of the most effective compounds of this class, 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide, on STIM1- and STIM2-mediated store-operated calcium entry and concluded that it blocks calcium entry through store-operated channels activated by both STIM1 and STIM2.</p>

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1,2,3,4-Dithiadiazole Derivative 3-(4-Nitrophenyl)-5-Phenyl-3H-1,2,3,4-Dithiadiazole-2-Oxide Affects Both STIM1- and STIM2-Dependent Store-Operated Calcium Channels

  • 期刊论文

  • 发表日期：

    2025年7月1日

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  • D. A. Grekhnev,
  • Iu. V. Novikova,
  • V. N. Yuskovets,
  • N. M. Chernov,
  • I. P. Yakovlev,
  • A. Yu. Skopin,
  • E. V. Kaznacheyeva,
  • V. A. Vigont

摘要

Disturbances in calcium signaling and, in particular, store-operated calcium entry are associated with a wide range of diseases, including neurodegenerative, oncological, and autoimmune pathologies. Inhibitors of store-operated calcium entry have a neuroprotective effect and suppress metastasis, which makes store-operated channels an attractive target for drug design. Previously, we showed that 1,2,3,4-dithiadiazole derivatives are negative modulators of store-operated calcium channels that are normally activated by STIM1 and STIM2 proteins. Here, we studied the specificity of action of one of the most effective compounds of this class, 3-(4-nitrophenyl)-5-phenyl-3H-1,2,3,4-dithiadiazole-2-oxide, on STIM1- and STIM2-mediated store-operated calcium entry and concluded that it blocks calcium entry through store-operated channels activated by both STIM1 and STIM2.