Dataset DUDE-Z served as the benchmark data set, encompassing 43 pharmaceutically relevant protein targets. Each target is represented by 26 (FA10) to 123 (PARP1) experimentally verified ligands (Figure ), with activities measured as EC50, IC50, Ki, or Kd values of 1 μM or better. For each active compound, the data set includes up to 50 carefully selected decoy molecules. These decoys are chosen based on property matching with the active compounds, considering physicochemical properties such as molecular weight, number of hydrogen bond donors and acceptors, number of rotatable bonds, and water-octanol partition coefficient (log P). As an improvement over previous versions of the benchmark data set, the DUDE-Z decoy matching procedure ensures that the active verified ligand and its corresponding decoys possess identical net charges at physiological pH. Additionally, to guarantee that the decoys exhibit dissimilar topology from the active compounds, only molecules with an ECFP4-based Tanimoto similarity of up to 0.35 to any active compound are chosen as decoys. In total, DUDE-Z comprises 2,312 unique active ligands and 69,994 decoy compounds across the 43 target proteins.