Targeted protein degradation (TPD) is revolutionizing therapeutic interventions by selectively eliminating disease-causing proteins using the body’s own mechanisms. Unlike traditional drugs that block protein functions, TPD recruits the cell’s ubiquitin-proteasome system to degrade targeted proteins. This novel approach has shown promising results, especially in treating diseases where conventional treatments have fallen short.
In recent years, advancements in TPD have introduced new strategies like proteolysis-targeting chimeras (PROTACs) and molecular glues. These innovative methods aim to enhance protein degradation by leveraging unique mechanisms to target specific proteins effectively. For instance, PROTACs simultaneously bind to a target protein and a ligase to induce degradation, while molecular glues trigger interactions for the same purpose.
“The key benefit of TPD is its ability to completely eliminate disease-causing proteins rather than just inhibiting them,”
explains an expert in pharmaceutical development. This precise targeting makes TPD a promising avenue for various medical fields such as oncology, neurology, and immunology where traditional approaches have faced limitations.
As per data from GlobalData’s Drugs database, there are currently 737 TPD drugs in development stages, with oncology being the primary focus followed by central nervous system disorders. While these developments are promising, challenges arise due to the larger molecular sizes of TPD drugs compared to traditional small molecules.
To address these challenges and ensure effective oral bioavailability of TPD medications,
experts emphasize the importance of formulation technologies.
Rebecca Coutts highlights that developing suitable orally available drugs requires understanding the physiochemical characteristics of each molecule and employing tailored approaches to improve solubility profiles.
“Strategies like micronisation and amorphous solid dispersions can significantly enhance solubility by modifying the drug substance structure,”
Coutts explains. By reducing particle size or changing crystalline materials into amorphous forms through techniques like spray drying, drug developers can optimize bioavailability for better patient outcomes.
Additionally, lipid-based formulations are being explored as a solution for improving solubility and permeability of high-molecular-weight molecules commonly found in TPD drugs. These formulations help enhance drug absorption while maintaining optimal solubility levels necessary for effective treatment delivery.
In collaboration with leading Contract Development Manufacturing Organizations (CDMOs) like PCI Pharma Services, advancements in TPD development continue to unlock new possibilities for targeted therapies. With specialized facilities and expertise in handling high-potency drugs, CDMOs play a crucial role in advancing drug development processes efficiently.
“CDMOs offer comprehensive solutions for enhancing targeted protein degrader development,”
notes Coutts from PCI Pharma Services. Their collaborative approach combined with technical capabilities ensures rapid progress from concept to clinical trials with a focus on overcoming formulation challenges effectively.
Looking ahead, further developments in particle engineering and solubility enhancement techniques are expected as the field evolves. These innovations will pave the way for more efficient delivery systems that can improve patient outcomes across diverse therapeutic areas benefiting from targeted protein degradation technologies.
