Chronically Acting CFTR Inhibitor Discovery for Secretory Diarrhea and ADPKD

Project Summary Abstract DiscoveryBioMed, Inc. (DBM) has launched an innovative and automation-friendly drug discovery program to screen a collection of small molecular compounds on a human epithelial cell platform expressing physiologically relevant levels of the wild-type Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) to discover a new class of therapeutic drugs for secretory diseases. CFTR plays a critical role in the regulation of Cl- transport and fluid secretion such that hyperactivity ofthe CFTR Cl- channel results in uncontrolled fluid secretion. Two CFTR-mediated diseases, secretory diarrhea and Autosomal Dominant Polycystic Kidney Disease (ADPKD), are driven in part by chronically active CFTR. These diseases demand treatment options that are effective and readily available due to their widespread impact on public health. Diarrheal illnesses are a leading cause of death worldwide. Despite the accepted practice of oral rehydration therapy, the incidence of secretory infection remains ala