Researchers at the University of Pittsburgh have identified Cytochrome c oxidase subunit 4 isoform 1 (Cox4i1) as a novel molecular target of metformin, a widely used antihyperglycemic agent. This discovery opens new avenues for the development of first-in-class small molecules for the treatment of diabetes, potentially revolutionizing diabetes therapy. The identification of Cox4i1 as a target could lead to more specific and efficacious treatments for both Type 1 and Type 2 diabetes.
Description
The technology is based on proteomic analysis of mouse liver protein isolates treated with metformin, revealing that Cox4i1 is stabilized via direct binding of the ligand. This binding limits the activity of Complex IV, leading to an increase in the AMP to ATP ratio and triggering AMP-Activated Protein Kinase (AMPK) activity. This dual mechanism is believed to contribute to the beneficial diabetes-related effects of metformin. The technology includes methods for drug screening against Cox4i1 to identify potential therapeutic compounds.
Applications
• Development of new antidiabetic drugs targeting Cox4i1
• Therapeutic intervention for Type 1 and Type 2 diabetes
• Drug screening for compounds that modulate Cox4i1 activity
Advantages
This technology provides a novel and rational explanation for the mechanism of action of metformin, identifies a new target for diabetes treatment, and opens opportunities for screening drug-like molecules against Cox4i1. The discovery of Cox4i1 as a target could lead to the development of more specific and effective treatments for diabetes, potentially worth billions of dollars.
Invention Readiness
The technology is currently at the in vitro data stage, with evidence of metformin binding to Cox4i1 obtained through proteomic analysis. Functional assays to show that metformin modulates the activity of Cox4i1 are underway and expected to be completed soon. The proteomics methods used have been validated in previous studies, demonstrating their effectiveness in discovering novel protein targets.
IP Status
https://patents.google.com/patent/US11519913B2
