Probe Criteria for Chemical Modulators vs PROTACs

Chemical Probes, small molecules designed to specifically modulate protein functions, are useful tools to study biological processes. PROTACS are hybrid molecule chimera which comprise a ligand and a peptide recognition motif for an E3 ligase. One side is targeting the protein of interest, the other draws in the target protein for ubiquitination and destruction by the proteasome.

These novel reagents exploit the ubiquitin-mediated proteasome degradation pathway to target the ligand-bound protein for intracellular degradation and represent an alternative to traditional modulators.

The dual modality of action effectively repurposes small molecule chemical tools to selectively degrade the target of interest.  

Here, we provide a set of criteria to choose the best PROTACs for you research and compare them with available chemical probes.