PPQ-102

Description: PPQ-102 (also known as CFTR Inhibitor) is a potent inhibitor of CFTR (cystic fibrosis transmembrane conductance regulator) discovered from screening of approximately 110000 small synthetic and natural compounds for inhibition of halide influx in CFTR-expressing epithelial cells. PPQ-102 can slow cyst enlargement in polycystic kidney disease and reduce intestinal fluid loss in secretory diarrheas. PPQ-102 completely inhibited CFTR chloride current with an IC50 of approximately 90 nM. Unlike prior CFTR inhibitors, PPQ-102 is uncharged at physiological pH, and therefore not subject to membrane potential-dependent cellular partitioning or block efficiency. Patch-clamp analysis confirmed voltage-independent CFTR inhibition by PPQ-102 and showed stabilization of the channel closed state. PPQ-102 prevented cyst expansion and reduced the size of preformed cysts in a neonatal kidney organ culture model of polycystic kidney disease. PPQ-102 is the most potent CFTR inhibitor identified to date.

References: J Med Chem. 2009 Oct 22; 52(20):6447-55. Eur Respir J. 2013 Dec; 42(6):1553-62. Am J Physiol Cell Physiol. 2011 Aug; 301(2):C289-303