Discovery of a Novel Hsp90 Inhibitor by Fragment Linking

Hooking up! Hsp90 is a molecular chaperone involved in the stabilisation of numerous client proteins including those involved in oncogenic transformations. Through a high‐throughput biochemical fragment screen, we have identified novel fragment inhibitors of Hsp90. Two fragment hits were combined to give a dual‐fragment Hsp90 complex, and the following successful fragment‐linking resulted in a 1000‐fold improvement in activity.