ethyl-1-(4-(2-3-3-trichloroacrylamido)phenyl)-5-(trifluoromethyl)-1h-pyrazole-4-carboxylate and Hypertrophy

ethyl-1-(4-(2-3-3-trichloroacrylamido)phenyl)-5-(trifluoromethyl)-1h-pyrazole-4-carboxylate has been researched along with Hypertrophy* in 1 studies

Other Studies

1 other study(ies) available for ethyl-1-(4-(2-3-3-trichloroacrylamido)phenyl)-5-(trifluoromethyl)-1h-pyrazole-4-carboxylate and Hypertrophy

ArticleYear
Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound.
    Proceedings of the National Academy of Sciences of the United States of America, 2009, Mar-31, Volume: 106, Issue:13

    Canonical transient receptor potential (TRPC) channels control influxes of Ca(2+) and other cations that induce diverse cellular processes upon stimulation of plasma membrane receptors coupled to phospholipase C (PLC). Invention of subtype-specific inhibitors for TRPCs is crucial for distinction of respective TRPC channels that play particular physiological roles in native systems. Here, we identify a pyrazole compound (Pyr3), which selectively inhibits TRPC3 channels. Structure-function relationship studies of pyrazole compounds showed that the trichloroacrylic amide group is important for the TRPC3 selectivity of Pyr3. Electrophysiological and photoaffinity labeling experiments reveal a direct action of Pyr3 on the TRPC3 protein. In DT40 B lymphocytes, Pyr3 potently eliminated the Ca(2+) influx-dependent PLC translocation to the plasma membrane and late oscillatory phase of B cell receptor-induced Ca(2+) response. Moreover, Pyr3 attenuated activation of nuclear factor of activated T cells, a Ca(2+)-dependent transcription factor, and hypertrophic growth in rat neonatal cardiomyocytes, and in vivo pressure overload-induced cardiac hypertrophy in mice. These findings on important roles of native TRPC3 channels are strikingly consistent with previous genetic studies. Thus, the TRPC3-selective inhibitor Pyr3 is a powerful tool to study in vivo function of TRPC3, suggesting a pharmaceutical potential of Pyr3 in treatments of TRPC3-related diseases such as cardiac hypertrophy.

    Topics: Amides; Animals; B-Lymphocytes; Calcium; Cell Line; Hypertrophy; Mice; Myocytes, Cardiac; NFATC Transcription Factors; Protein Transport; Pyrazoles; Rats; Structure-Activity Relationship; TRPC Cation Channels; Type C Phospholipases

2009