Large-scale cell screening uncovers molecular glues that trigger protein degradation

Cells constantly monitor and recycle their proteins through a tightly regulated waste-disposal system. Proteins that are no longer needed are tagged and broken down by specialized cellular machinery. Recent advances in drug discovery seek to exploit this system by redirecting it toward disease-relevant targets. This strategy relies on so-called molecular glues, small molecules that induce interactions between proteins that would not normally bind to each other. If a disease-causing protein can be brought into contact with a cellular degradation enzyme, it is selectively eliminated by the cell itself. Until now, however, most molecular glues have been discovered by chance, limiting their broader therapeutic application.