Table 1 A comparison among different generations of PROTACs
From: Protein degradation technology: a strategic paradigm shift in drug discovery
| Â | 1st generation | 2nd generation | 3rd generation |
|---|---|---|---|
Advantages | Larger contact interface with POI and more choices of modification on the drug | Applicable for “undruggable” targets; good cell permeability and solubility | Well-controllable biological characters; causing protein degradation in a highly specific temporal and spatial manner |
Disadvantages | Poor cell permeability and stability [18] | Potential off-target effects, relatively high molecular weight, and toxicity [18, 21, 23, 24] | Potential damage to DNA by UV light and low tissue penetration [18, 27] |