Repurposing Drugs for ADPKD: Assay Development and High-throughput Screening

Authors

• C Danchik
• R Asawa
• A Zakharov
• M Boutin
• J Trott
• D Wallace
• A Simeonov
• R Weiss
• N Martinez

Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most commonly inherited renal disorder with a prevalence of 1:400 to 1:1,000. It is characterized by the formation of numerous fluid-filled cysts in both kidneys, which leads to kidney failure and death. Despite being the most commonly inherited kidney disease, there is currently no approved treatment in the United States. ADPKD is caused by a mutation in one of two genes: PKD1 (85%) which encodes polycystin-1 or PKD2 (15%) which encodes polycystin-2. These proteins are present in the cell membrane and play roles in diverse cellular function ranging from proliferation to fluid secretion to Ca2+ signaling. Mutations in PKD1 or PKD2 result in increased renal epithelial cell proliferation as well as upregulation of many cancer-relevant signaling proteins. Furthermore, defective glucose metabolism observed in ADPKD is reminiscent of the Warburg effect in cancer. Because of the similarities between ADPKD and cancer, repurposing cancer drugs for ADPKD is an appealing option. We aim to explore drug repurposing for ADPKD through the development of biologically relevant in vitro assays amenable for high-throughput screening of oncology-focused small molecule collections.

Scientific Focus Area: Chemical Biology

This page was last updated on Friday, March 26, 2021