Award Details:
Award Type: Accelerator
Award #: A-018
Proposal Title: Development of Small Molecule Inhibitors of Gα12/ Alpha-SNAP-dependent vWF Secretion
PI(s): Richard Minshall (UIC)
Award Amount: $100,000.00
Application Cycle: Round 5 (Fall 2021)
Award Start Date: October 1, 2021
Award End Date: September 30, 2022
Abstract:
Patients with cancer, sickle cell disease, type 2 diabetes, severe infections, atrial fibrillation, among others, are at increased risk of developing blood clots that can lead to heart attack, stroke, or organ failure. Inflammation associated with these diseases increase von Willebrand factor (vWF) secretion from endothelial cells, which is the glue to which platelets adhere to form a clot. This project aims to develop a drug that blocks vWF secretion and thereby prevents blood clots from forming in high-risk individuals. Based on our discovery of the mechanism that leads to vWF secretion from endothelial cells, we optimized a competitive binding fluorescent high throughput screening assay based on a high affinity protein-protein interaction. We will use this assay to identify and develop initial hits into lead compounds with the goal of establishing a novel class of pharmacological inhibitors of vWF secretion for preventing microvascular thrombosis and cardiovascular complications of disease.