Fig. 4. Applications of activity-directed synthesis. ADS is a function-driven approach where bioactive molecules emerge in tandem with their associated synthetic routes, through iterative rounds of activity optimisation. Panel A: ADS was used to discover AR modulators based on scaffolds with no previously annotated AR activity. Panel B: ADS was used to “grow” a known fragment to yield structurally-diverse ligands with increased activity against AR. Panel C: Structures of recently-reported inhibitors of the p53/hMDM2 interaction discovered through ADS. AR: Androgen receptor.
