Towards the Minimization of ADMET Liabilities: Scaffold Hopping and Hit Expansion in Trillion-Sized Compound Spaces in 2D and 3D

Small molecules are a cornerstone of modern medicine, representing most approved therapeutics, with a consistent rise in new approvals. In drug discovery, hit expansion and scaffold hopping are pivotal strategies for identifying structurally novel lead candidates that mimic the function of known active compounds. These approaches are essential for initiating new medicinal chemistry programs, as they provide pathways to secure novel intellectual property and mitigate or resolve liabilities related to ADMET.