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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

  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