Biochem/physiol Actions

Reversible: yes

Primary TargetTMEM16A-CaCC

General description

A cell-permeable uricosuric agent that, in addition to its known efficacy in gout treatment, acts as a reversible CaCC blocker and is reported to be more potent than NFA (Cat. No. 481987) and NPPB (Cat. No. 484100) in suppressing 500 nM Ionomycin- (Cat. Nos. 407950, 407952, and 407953) induced I^- influx in TMEM16A-expressing HEK293 cells (IC₅₀ = 9.97, 140, and 150 µM, respectively) as well as in blocking voltage-gated Cl^- current in TMEM16B-expressing HEK293 cells, while exhibiting much reduced potency against ENaC (α, β, and γ) or CFTR. Shown to significantly reduce mucin secretion from NHBE (normal human bronchial epithelial) and suppress human ASM (airway smooth muscle) contraction upon muscarinic receptor stimulation.

A cell-permeable uricosuric agent that, in addition to its known efficacy in gout treatment, acts as a reversible CaCC blocker and is reported to be more potent than NFA (Cat. No. 481987) and NPPB (Cat. No. 484100) in suppressing 500 nM Ionomycin- (Cat. Nos. 407950, 407952, and 407953) induced I^- influx in TMEM16A-expressing HEK293 cells (IC₅₀ = 9.97, 140, and 150 µM, respectively) as well as in blocking voltage-gated Cl^- current in TMEM16B-expressing HEK293 (64% inhibition with 10 µM BBR vs. 47% inhibition with 300 µM NFA; by whole cell patch clamp), while exhibiting much reduced potency against voltage-gated current via ENaC (α, β, and γ) or CFTR (by 25% and 17% with 10 µM BBR, respectively, using HEK293 ENaC or CFTR transfectants). Shown to significantly reduce 100 µM ATP-induced CaCC current (IAC current = 1.137 vs. 3.099 µA/cm² with or without 10 µM BBR) and mucin secretion from NHBE (normal human bronchial epithelial) as well as suppress human ASM (airway smooth muscle) contraction upon muscarinic receptor stimulation.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Due to the nature of the Hazardous Materials in this shipment, additional shipping charges may be applied to your order. Certain sizes may be exempt from the additional hazardous materials shipping charges. Please contact your local sales office for more information regarding these charges.

Kobayashi, K., et al. 2012. Drug Metab. Pharmacokinet. In press.Zhang, C.H., et al. 2013. Am. J. Respir. Crit. Care Med.187, 374.Huang, F., et al. 2012. Proc. Natl. Acad. Sci. USA.109, 16354. Fujimori, S., et al. 2011. Nucleosides Nucleotides Nucleic Acids30, 1035.Perez-Ruiz, F., et al. 1998. Ann. Rheum. Dis.57, 545.

Packaging

Packaged under inert gas

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Toxic (F)