Chemical structures were encoded as eight different fingerprints, namely extended connectivity fingerprints ECFP4 and ECFP6, the MinHashed Fingerprint MHFP6, the RDKit Atom-Pair Fingerprint (AP), the Macromolecule Extended Fingerprint (MXFP), the MinHashed Atom-Pair fingerprint MAP4, the Molecular ACCess System keys (MACCS), and Molecular Quantum Numbers (MQNs). 45 ECFP4, ECFP6, AP, MACCS and MQN were calculated using the implementation in the RDKit package (2022.3.4. , ). ECFPs were calculated as 2048-bit vectors. MHFP6 and MAP4 were calculated as 2048-bit vectors using the code described in and . MXFP was calculated using a new open-source version available at group/mxfp_python. The differential reaction fingerprint (DRFP) was calculated as 2048-bit vectors using the code available at . Pairwise distances for every possible molecular pair were calculated and stored as a matrix for each fingerprint. Distances were calculated as Jaccard distances (dJ) for ECFP4, ECFP6, MHFP6, AP, MAP4 and MACCS keys, and as Taxicab distances (dT) for MXFP and MQNs, with values min-max standardized. We selected similar pairs by applying the following distance threshold: dJ < 0.6 for ECFP4, ECFP6, MHFP6, dJ < 0.5 for AP, dJ < 0.2 for MACCS, dJ < 0.8 for MAP4, dT < 0.1 for MXFP and dT < 0.05 for MQN (Taxicab distances after rescaling) for the FDA set and dJ < 0.2 for ECFP4, ECFP6, MHFP6, AP, dJ < 0.0125 for MACCS, dJ < 0.3 for MAP4, dT < 0.1 for MXFP and dT < 0.05 for MQN for the EGFR and PMB sets.