Bioorthogonal Activation of PROTAC Prodrugs

Case ID:

Utilizing proteolysis targeting chimeras (PROTACs) to degrade proteins that are important for tumorigenesis has become a potential therapeutic strategy for cancer. This innovation is an on-demand prodrug strategy called click-release proteolysis targeting chimeras, or “crPROTACs.” The crPROTACs strategy utilizes bioorthogonal chemistry and a cancer biomarker integrin-targeted ligand for targeted release of the PROTAC prodrugs, resulting in selective degradation of proteins of interest (POIs) in cancer cells while sparing normal cells. This approach allows for precise control over the degradation activity of PROTACs, minimizing potential toxicity and side effects, while providing a versatile and non-biological method to achieve selective protein degradation in cancer cells.

In recent clinical studies, a new therapeutic approach called proteolysis targeting chimeras (PROTACs) has shown great promise. However, concerns have arisen regarding the potential toxicity and unintended effects caused by uncontrolled protein degradation and off-target effects. The newly developed crPROTACs strategy offers a solution by enabling precise and on-demand activation of PROTAC prodrugs in cancer cells, thus improving upon current methods by addressing concerns related to toxicity and off-target effects. 


  • Precision cancer therapy
  • Therapeutic customization


  • Enhanced specificity
  • Reduced toxicity 
Patent Information:
Contact For More Information:
Garrett Edmunds
Licensing Manager, UAHS-TLA
The University of Arizona
Lead Inventor(s):
Wei Wang
Mengyang Chang
Giri Gnawali