PROTACs ® & Protein Degradation

Targeted protein degradation using Proteolysis Targeting Chimeras, or PROTAC ®, is a new and promising therapeutic method in drug discovery. PROTACs have the ability to regulate protein degradation through targeted control of ubiquitin E3 ligases. This novel technology allows for the degradation of disease-related proteins and offers many advantages over traditional protein inhibition.

PROTACs function by hijacking the final action of E3 ligases and subsequently tagging the protein of interest for ubiquitination. A PROTAC is composed of three parts; an E3 ligand that binds to an E3 ligase, a ligand that binds to the protein of interest, and a linker connecting the two ligands. When each ligand binds its respective partner, it triggers ubiquitination of the protein of interest. The PROTAC itself is not degraded by this process, making PROTACs a valuable tool for mediating protein degradation. A single PROTAC can promote the degradation of many subsequent proteins and functions substoichiometrically.

Advantages

• Promotes degradation that circumvents the native resistance of proteins against sustained inhibition
• Select weak binding and promiscuous ligands can be utilized with PROTACs and still demonstrate high degradation efficacy
• Ineffectual ligands which do not modulate the cellular functions of the protein of interest can be used to mediate degradation through PROTACs
• PROTACs could have the ability to degrade proteins previously believed to be 'undruggable' through conventional small molecule inhibition

PROTAC Products and Services

BPS Bioscience is a leading product manufacturer and service provider in the PROTAC space. Available services include

• Homogeneous proximity assays to assess the chemical adaptorfunction of PROTACs

PROTAC ® is a registered trademark of Arvinas Operations Inc., and is used under license.