Intrinsically disordered proteins and biomolecular condensates as drug targets

Intrinsically disordered domains represent attractive therapeutic targets because they play key roles in cancer, as well as in neurodegenerative and infectious diseases. They are, however, considered undruggable because they do not form stable binding pockets for small molecules and, therefore, have not been prioritized in drug discovery. Under physiological solution conditions many biomedically relevant intrinsically disordered proteins undergo phase separation processes leading to the formation of mesoscopic highly dynamic assemblies, generally known as biomolecular condensates that define environments that can be quite different from the solutions surrounding them. In what follows, we review key recent findings in this area and show how biomolecular condensation can offer opportunities for modulating the activities of intrinsically disordered targets.

Automated summary

Intrinsically disordered domains are attractive therapeutic targets in cancer, neurodegenerative, and infectious diseases, despite being considered undruggable. Recent findings suggest that biomolecular condensation processes can offer opportunities for modulating the activities of intrinsically disordered targets in a different environment from their surrounding solutions.