1160514-60-2

Pyr3 (1160514-60-2) is a selective blocker of the TRP canonical 3 channel (TRPC3)1 which can function as a receptor-operated channel2. A useful tool for dissecting GPCR-downstream signaling mechanisms.3 Pyr3 may be effective in reducing cardiac hypertrophy.2

Pyr3 is a pyrazole derivative that is used to discriminate between (transient receptor potential cation) TRPC4 mediated receptor operated calcium entry and STIM1/Ora1 mediated store operated calcium entry pathway in human embryonic kidney and rat mast cells.

A cell-permeable pyrazole that acts as an equally potent blocker of Stim1 and Orai1-coupled CRAC (Ca²⁺ release-activated Ca²⁺) channel-mediated SOCE (store-operated Ca²⁺ entry) in RBL-2H3 cells (IC₅₀ = 540 nM by Fura-2; peak current density pA/pF = -1.45 and -7.50, respectively, with or without 3 μM BTP2/Pyr3 by whole cell clamp) and the transient receptor potential cation channel TRPC3-mediated ROCE (receptor-operated Ca²⁺ entry) in TRPC3-expressing HEK293 cells (IC₅₀ = 540 nM; by Fura-2; pA/pF = -2.27 and -18.50, respectively, with or without 3 μM BTP2/Pyr3). Pyr3 is also demonstrated to alleviate pressure overload-induced cardiac hypertrophy following TAC (transverse aortic constriction) operation in mice (0.1 mg/kg/day via i.p. osmotic pump) in vivo. A great complement to Pyr 2 (Cat. No. 203890), Pyr6, and Pyr10 in Ca^{2+ signaling studies.}

Pyr3 is a pyrazole compound that potently and selectively antagonizes TRPC3. Pyr3 inhibits TRPC3 by binding to the extracellular side of the receptor, resulting in suppression of B cell activation and cardiac hypertrophy.Members of the canonical transient receptor potential (TRPC) channel family are ion channels which conduct Ca+2 and are activated by membrane receptor-mediated stimulation of phospholipase C (PLC) activity. However, TRPC3 and other family members are also activated by membrane-independent diacylglycerol (DAG). BTP1 and BTP2 are pyrazoles that block TRPC channels, but they are not specific for TRPC subtypes. This channel is implicated in various processes, including B cell receptor (BCR)-mediated Ca+2 oscillations, activation of nuclear factor of activated T cells (NFAT), and promotion of cardiac hypertrophy.

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1) Kiyonaka et al. (2009), Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound; Proc. Natl. Acad. Sci. USA., 106 5400 2) Eder and Molkentin (2011), TRPC channels as effectors of cardiac hypertrophy; Circ. Res., 108 265 3) Sabourin et al. (2012), Activation of transient receptors potential canonical 3 (TRPC3)-mediated CA2+ entry by A1 adenosine receptor in cardiomyocytes disturbs atrioventricular conduction; J. Biol. Chem., 287 26688