Novel pyrazole inhibitors for discrimination between receptor-operated and store-operated Ca2+ entry
© Schleifer et al; licensee BioMed Central Ltd. 2011
Published: 5 September 2011
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.
We tested a series of pyrazol compound structurally related to Pyr3 , 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.
Supported by the Austrian Science Fund FWF project P21925-B19 and P21118-B09.
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