Activity cliff identification and labelling. Activity cliffs were identified using the criteria established in MoleculeACE. Initially, comprehensive structural similarities between molecule pairs targeting the same protein were calculated. This included combining the Tanimoto coefficient for all-atom molecule fingerprints and scaffold molecule fingerprints, along with the Levenshtein distance of SMILES sequences. Molecule pairs exhibiting a structural similarity greater than 0.9 were identified. Subsequent bioactivity value checks filtered out those structurally similar pairs that exhibited a negative log bioactivity value difference greater than 2 (equivalent to a 100-fold difference in nM units). Pairs meeting these criteria were labelled as AC data, while others were classified as non-AC data.