This technology involves novel compounds comprising an amine and thiouracil core that selectively target cytochrome b5 reductase 3 (Cyb5R3) to regulate nitric oxide (NO) signaling and cyclic guanosine monophosphate (cGMP) production. Identified via a pharmacophore-based screening approach using propylthiouracil as a template, these compounds are designed to compete with NADH at the Cyb5R3 binding site. Acute dosing induces vasodilation, enhancing blood flow and reducing blood pressure, while chronic dosing reverses these effects, leading to vasoconstriction. Structure-activity relationship studies have detailed how modifications of the core and aryl groups influence potency, providing a clear pathway for further structural optimization.
Description
What distinguishes this technology is its dual-phase action profile and the precision with which it modulates vascular tone. The compounds' ability to deliver contrasting therapeutic outcomes—beneficially adjusting blood flow under different conditions—and the integration of a novel assay method to measure Cyb5R3 activity highlight its clinical promise. Comprehensive experimental evidence supports direct interactions with oxidized soluble guanylate cyclase, establishing a robust framework for future applications in managing cardiovascular, inflammatory, and vascular disorders.
Applications
- Bleeding disorder treatment
- Vasodilator cardiovascular therapy
- Cyb5R3 diagnostic assay kit
- Myocardial infarction therapy
- Erectile dysfunction treatment
Advantages
- Enables precise modulation of vascular tone by targeting Cyb5R3, which is critical for nitric oxide signaling and blood pressure regulation.
- Offers dual therapeutic strategies: acute Cyb5R3 inhibition promoting vasodilation to treat bleeding disorders and other trauma-related issues, and activation to address conditions like hypertension and diabetic vasculopathy.
- Utilizes pharmacophore-based screening and structure–activity relationship studies for optimizing compound potency and specificity.
- Provides a novel assay method for measuring Cyb5R3 activity, facilitating both research and the development of targeted therapies.
IP Status
https://patents.google.com/patent/US10568886B2
