High Throughput Screening Assay for Anti-Cancer and Cardiac Drugs
Project ID: D2012-13Novelty:The technology comprises a novel assay to screen drug molecules against cancer, congestive cardiac failure and other Na/K-ATPase/Src receptor complex mediated diseases.Value Proposition: Research has revealed that Na/K-ATPase/Src receptor complex is involved in cell-signal transduction mechanisms. Initiation or inhibition of this receptor complex affects the downstream protein kinase cascades and regulates cell growth, renal cell salt handling, and organ remodeling. This discovery can be utilized to develop novel therapeutics for the treatment of different diseases such as cancer, chronic renal diseases, and congestive heart failures. The disclosed invention entails a simple FRET – based in vitro high throughput assay to screen drug molecules against this receptor complex target for discovering new agonists and antagonists of this receptor complex. Description:Dr. Zijian Xie’s laboratory at The University of Toledo has demonstrated that mammalian cell Na/K-ATPase interacts with various membranes and cytoplasmic proteins, thus serving as a classic signaling receptor. Specifically, the inventors have identified that Na/K-ATPase forms a receptor complex with Src enzyme and regulates cell growth, differentiation, apoptosis, and fibrosis. They have further demonstrated that activation of this Na/K-ATPase/Src receptor complex by physiological concentrations of cardiotonic steroids play important roles in regulation of renal, cardiac, and vascular functions. Moreover, sustained activation of this receptor complex result in ROS stress that contributes to many diseases including cancer, hypertension, preeclampsia, chronic stage renal diseases, congestive heart failure, thus resulting in the use of this complex as therapeutics target for the above mentioned diseases. Accordingly, the inventors have developed a protocol to screen positive and negative regulatorsagonists and antagonists of this novel receptor complex. This FRET-based assay utilizes in vitro constitution of the receptor complex. The binding of agonists/antagonists to the receptor complex initiates/inhibits the complex activity that can be measured by a peptide-based FRET analysis. The inventors have also cell-based assays to confirm the activation/inhibition of the receptor complex.Application: Development of new drugs against cancer, renal diseases, and cardiac failuresIP Status: Patent pending
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