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Novel pyrazole inhibitors for discrimination between receptor-operated and store-operated Ca2+ entry

Background

Calcium governs a wide range of cellular processes. Specifically, control of gene transcription involves Ca2+ entry channels that are activated by either voltage, second messengers or depletion of intracellular stores. The family of classical transient receptor potential channels (TRPC) has been implicated in both the receptor/second messenger as well as in store-operated Ca2+ entry pathway, and represents an attractive target for therapeutic intervention.

Methods

We tested a series of pyrazol compound structurally related to Pyr3 [1], a recently discovered TRPC3 inhibitor, for effects on receptor- as well as store-operated Ca2+ entry into RBL-2H3 mast cells and HEK293 cells overexpressing TRPC3.

Results and conclusions

We identified novel Ca2+ entry inhibitors, which are able to discriminate between the two tightly related pathways of receptor/second messenger-activated and store-operated calcium entry. These compounds appear suitable for selective modulation of Ca2+-dependent gene transcription in a variety of mammalian cells.

References

  1. 1.

    Glasnov TN, Groschner K, Kappe CO: High-speed microwave-assisted synthesis of the trifluoromethylpyrazol-derived canonical transient receptor potential (TRPC) channel inhibitor Pyr3. ChemMedChem. 2009, 4: 1816-1818. 10.1002/cmdc.200900304.

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Acknowledgements

Supported by the Austrian Science Fund FWF project P21925-B19 and P21118-B09.

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Correspondence to Klaus Groschner.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Schleifer, H., Oppenrieder, R., Stürmer, S. et al. Novel pyrazole inhibitors for discrimination between receptor-operated and store-operated Ca2+ entry. BMC Pharmacol 11, A18 (2011). https://doi.org/10.1186/1471-2210-11-S2-A18

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Keywords

  • Mast Cell
  • Gene Transcription
  • HEK293 Cell
  • Pyrazole
  • Intracellular Store