University of Pittsburgh researchers have designed innovative nucleotide prodrugs that leverage boryl allyl phosphate groups to selectively target oxidative stress environments. These prodrugs remain inactive until they encounter high levels of hydrogen peroxide, a common marker in diseased tissues such as cancer and viral infections. This targeted activation mechanism ensures that the active nucleotides are released specifically in diseased cells, minimizing off-target effects and enhancing therapeutic efficacy.
Description
This technology involves the development of nucleotide prodrugs that incorporate boryl allyl phosphate groups. These groups are sensitive to hydrogen peroxide, which is abundant in areas of high oxidative stress. Upon exposure to hydrogen peroxide, the prodrugs undergo oxidative cleavage, releasing active nucleotides directly in the diseased tissues. This selective activation mechanism allows for precise targeting of diseased cells while sparing healthy tissues, making it a promising approach for treating conditions associated with oxidative stress.
Applications
1. Cancer treatment
2. Anti-viral development
3. Treatment of other diseases linked to oxidative stress
Advantages
The novel nucleotide prodrugs offer significant advantages. Their selective targeting mechanism activates the prodrugs specifically in high oxidative stress environments, reducing off-target effects and systemic toxicity. This targeted release enhances safety compared to traditional nucleotide prodrugs. Customizable release kinetics allow optimization based on therapeutic needs, ensuring desired potency and efficacy. The versatile platform is applicable to various phosphate-containing therapeutics, including anticancer and antiviral agents, and demonstrates proven compatibility with enzymatic systems. The boryl allyl phosphate approach represents a major advancement in prodrug chemistry, overcoming limitations of existing technologies for more effective treatments.
Invention Readiness
Currently in the concept phase, these nucleotide prodrugs have shown promising results in vitro. Further research is required to test their efficacy in vivo. The technology is supported by a robust patent application and ongoing research efforts to optimize and validate the prodrugs for clinical use.
IP Status
https://patents.google.com/patent/WO2024167952A1
