A Pyrazole Derivative, YM-58483, Potently Inhibits Store-Operated Sustained Ca2+ Influx and IL-2 Production in T Lymphocytes

A Pyrazole Derivative, YM-58483, Potently

A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine production by facilitating transient receptor potential melastatin 4 channel activity.

3,5-Bis(trifluoromethyl)pyrazole derivative (BTP2) or N-[4-3, 5-bis(trifluromethyl)pyrazol-1-yl]-4-methyl-1,2,3-thiadiazole-5-carboxamide (YM-58483) is an immunosuppressive compound that potently inhibits both Ca2+ influx and interleukin-2 (IL-2) production in lymphocytes. We report here that BTP2 dosedependently enhances transient receptor potential melastatin 4 (TRPM4), a Ca2+-activated nonse...

A Pyrazole Derivative Potently Inhibits Lymphocyte Ca Influx and Cytokine Production by Facilitating Transient Receptor Potential Melastatin 4 Channel Activity

3,5-Bis(trifluoromethyl)pyrazole derivative (BTP2) or N-[4–3, 5-bis(trifluromethyl)pyrazol-1-yl]-4-methyl-1,2,3-thiadiazole-5carboxamide (YM-58483) is an immunosuppressive compound that potently inhibits both Ca influx and interleukin-2 (IL-2) production in lymphocytes. We report here that BTP2 dosedependently enhances transient receptor potential melastatin 4 (TRPM4), a Ca -activated nonselect...

Sphingomyelinase D inhibits store-operated Ca2+ entry in T lymphocytes by suppressing ORAI current

Infections caused by certain bacteria including Mycobacterium tuberculosis and Corynebacterium pseudotuberculosis provoke inflammatory responses characterized by the formation of granulomas with necrotic foci-so-called caseous necrosis. The granulomas of infected animals show prominent infiltration by T lymphocytes, and T cell depletion increases host mortality. Notorious zoonotic C. pseudotube...

Potent inhibition of store-operated Ca2+ influx and superoxide production in HL60 cells and polymorphonuclear neutrophils by the pyrazole derivative BTP2.

Store-operated calcium entry (SOCE) is a key regulator in the activation of leukocytes. 3,5-Bistrifluoromethyl pyrazole (BTP) derivatives have been identified recently as inhibitors of T lymphocyte activation. The inhibitory effect of one of these compounds, N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide (BTP2), appears to be a result of inhibiti...