UT Health San Antonio Innovates Breakthrough in Drug Discovery
Researchers at UT Health have achieved a significant breakthrough through a novel concept known as "chemical endocytic medicinal chemistry," which aims to transform how drugs are designed for cellular uptake. The key to this discovery is CD36, a protein receptor found on many cell surfaces. The team developed a method to enhance the interaction between drugs and CD36, allowing larger and more polar compounds to enter cells more effectively.
This new strategy could potentially enable drugs that are typically administered intravenously to be taken orally and help them cross the blood-brain barrier. This has wide-reaching implications for treating conditions such as brain cancer and dementia, expanding the range of available treatments for these conditions.
For many years, small-molecule drugs were limited by the "Rule of 5," which suggested that compounds larger than 500 Daltons (Da) could not be effectively absorbed by cells. The team's work challenges this idea by showing that larger molecules, when optimised for CD36-mediated uptake, can successfully enter cells. This breakthrough could greatly increase the range of compounds that can be developed into therapeutic drugs.
The research also focused on proteolysis-targeting chimeras (PROTACs), which are large molecular compounds designed to target specific proteins. The team demonstrated that optimising CD36 activity improved the uptake of PROTACs, achieving faster and more effective drug delivery.
The study’s findings were independently verified by multiple research teams, confirming the robustness and reliability of the results. This discovery represents a significant shift in how drugs may be developed, as it moves away from relying on passive diffusion and instead harnesses the potential of receptor-mediated cellular entry.
The implications of this research extend beyond drug development. By considering how different individuals express CD36, particularly in cancer tissues, it may be possible to tailor treatments based on a patient’s unique biological profile, leading to more precise and effective therapies.
Overall, this advancement could reshape the future of drug discovery, development, and clinical application, potentially changing how regulatory bodies like the FDA evaluate and approve new treatments.
