While for optimizing a chemical series, it is only necessary to investigate the local chemical space around the series, for scaffold hopping it is important to span the whole desirable chemical space and in addition, not waste time generating molecules outside the desirable domain. Therefore, the proposed benchmark will be especially important for scaffold hopping to ensure that the model explores as much of the desired chemical space as possible, while minimizing sampling of undesirable compounds. all canonical SMILES of GDB-13 molecules (dark blue) and the training set (black). Note that the relative sizes of the different subsets do not reflect their true size.