Table 3 The advantages and disadvantages of covalent and noncovalent PPI inhibitors
From: The design and development of covalent protein-protein interaction inhibitors for cancer treatment
| Â | Advantages | Disadvantages |
|---|---|---|
Covalent PPI inhibitors | Longer duration of action Lower prolonged systemic exposure Higher potency and selectivity Higher biochemical efficiency Less sensitive to pharmacokinetic parameters Computational prediction of reversible covalent binding Lower risk of drug resistance | Off-target toxicity Potential immunogenicity of the resulting target adducts |
Non-covalent PPI inhibitors | Larger non-covalent compound libraries Long dissociated half-lives Less off-target toxicity | Not very selective Usually weak reactivity Limit to non-covalent binding affinity Not very potent |