PROteolysis-TArgeting Chimeras (PROTACs) are heterobifunctional small molecules that leverage the ubiquitin-proteasome system (UPS) to selectively degrade disease-relevant proteins. Unlike traditional inhibitors that block protein function, the unique ability of PROTACs to degrade target proteins offers a powerful approach for sustained protein depletion. PROTACS are particularly attractive in oncology, where their mechanism of action presents opportunities to overcome drug resistance and target previously “undruggable” proteins. As a result, several PROTAC-based therapies are under clinical investigation, including notable candidates such as ARV-110 for prostate cancer and ARV-471 for breast cancer.

Despite their promise, PROTACs often suffer from issues such as poor tissue penetration and limited intracellular uptake due to their complex physicochemical properties. Improving targeted delivery therefore remains a significant goal in their development.

Learn how researchers overcome this challenge by developing tumor-targeted nanoparticles specifically designed to enhance delivery of PROTACs to colorectal cancer cells.