Researchers at EPFL have achieved a ninefold increase in the bioavailability of certain drugs aimed at stroke prevention. The findings, published in Nature Chemical Biology, point toward the development of oral medications for a range of diseases, marking a potential shift in how these therapies are delivered to patients in North America and beyond.
Many diseases have clearly identified target molecules. Inhibiting these targets with drugs can cure, ease symptoms, or slow disease progression. Yet most therapeutic compounds are small, flat molecules that struggle to bind effectively to larger, complex targets. While protein-based drugs can address this gap, their need for injections limits their practicality for long-term treatment.
In the new study, scientists demonstrate that cyclic peptides, compact circular molecules built from the same amino-acid blocks as larger proteins, can engage challenging targets when taken orally. Historically, these molecules faced two major hurdles: quick digestion in the gut and poor absorption. To enhance their stability, researchers introduced thioester bonds into the cyclic peptide structures.
Animal testing showed that these redesigned peptides achieved oral bioavailability as high as 18 percent. In practical terms, about one in five molecules reached the bloodstream and produced a therapeutic effect. This is a striking improvement over typical oral bioavailability for cyclic peptides, which often falls below 2 percent, and it signals a meaningful advance in oral peptide medicines.
In the experiments, the cyclic peptides targeted thrombin, a protein central to the blood-clotting cascade. By modulating thrombin activity, such agents hold promise for preventing and treating thrombotic conditions, including stroke and myocardial infarction. The researchers emphasize that the approach is broadly adaptable: the same strategy could be applied to a wide array of protein targets, potentially accelerating treatments across several disease areas.
Experts associated with the work caution that while the results are encouraging, further development is needed to translate these findings into safe and effective therapies for people. Nevertheless, the study provides a clear blueprint for how oral peptide drugs might be designed to engage complex targets and achieve clinically relevant exposure. The universal aspect of the method suggests it could catalyze new options in drug discovery and partially redefine what is possible with oral biologics, according to this study attributed to EPFL researchers and published in Nature Chemical Biology in 2024.
Overall, the research underscores a shift toward orally available protein-like drugs that can reach targets previously thought inaccessible to small molecules. If validated through additional studies and clinical trials, cyclic peptides enhanced with thioester chemistry may widen the landscape of therapies available for stroke prevention and beyond, offering patients more convenient and effective treatment options.