Researchers at the University of Pittsburgh and the University of Pennsylvania have identified Profilin1 (Pfn1) as a novel therapeutic target for atherosclerosis. Pfn1, an actin-binding protein, is upregulated in atherosclerotic plaques. The team has developed small molecule inhibitors of Pfn1-actin interaction, demonstrating potential anti-angiogenic effects and proposing their use as a novel therapy for atherosclerosis.
Description
Profilin1 (Pfn1) is an actin-binding protein whose activity is crucial for actin polymerization. Researchers have developed small molecule inhibitors targeting the Pfn1-actin interaction, with the lead candidate molecule C74 showing the ability to reverse Pfn1’s effect on actin polymerization in vitro. A more robust second-generation compound, KX6, has also been generated. Genetic evidence suggests that inhibition of Pfn1 could be atheroprotective, making these inhibitors promising candidates for treating atherosclerosis.
Applications
- Therapeutic intervention for atherosclerosis
- Anti-angiogenic therapy
- Research tool for studying actin dynamics and atherosclerosis
Advantages
This technology targets the Pfn1-actin interaction, a novel mechanism with demonstrated anti-angiogenic effects. There are currently no known resistance mechanisms to Pfn1-actin inhibition, making it a promising therapeutic approach. The development of second-generation compounds like KX6 enhances the robustness and potential efficacy of this therapy.
Invention Readiness
The technology is supported by in vivo data demonstrating the potential of Pfn1 inhibitors in reversing actin polymerization effects. The lead candidate molecule C74 and the second-generation compound KX6 have shown promising results in vitro. Further studies are planned to test these inhibitors in the context of atherosclerosis.
