More than 300,000 Protein-Protein Interactions (PPIs) can be found in human cells. This number is significantly larger than the number of single proteins, which are the classical targets for pharmacological intervention. Hence, specific and potent modulation of PPIs by small, drug-like molecules would tremendously enlarge the "druggable genome" enabling novel ways of drug discovery for essentially every human disease. This strategy is especially promising in diseases with difficult targets like intrinsically disordered proteins or transcription factors, for example neurodegeneration or metabolic diseases. Whereas the potential of PPI modulation has been recognized in terms of the development of inhibitors that disrupt or prevent a binary protein complex, the opposite (or complementary) strategy to stabilize PPIs has not yet been realized in a systematic manner.

 

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