CFTR Channel Pharmacology : Novel Pore Blockers Identified by High-throughput Screening

Investigators of anion channels are frequently heard bemoaning the absence of potent, specific inhibitors of their favorite channel. The lack of such blockers has been particularly frustrating for researchers investigating the cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel, which plays a central role in electrolyte transport across epithelial tissues (Welsh et al., 2001). Perhaps the complaints of CFTR researchers might soon be a thing of the past following the discovery of glycine hydrazides by Chatchai Muanprasat and colleagues, which is reported in this issue of the Journal of General Physiology (Muanprasat et al., 2004). In brief, the authors employ a high-throughput screening (HTS) assay for the identification of CFTR inhibitors to discover glycine hydrazides and then investigate the effects of these agents on CFTR function in experiments that range from single channels to animal models (Muanprasat et al.,...