This high accuracy for the early time point could have been related to the setting of the transit compartment, which can induce the transition phase of compounds . The high accuracy of the late time point could have been due to the setting of the deep brain compartment. These results are in agreement with the reported brain trapping of basic compounds in lysosomes . We actually observed weak positive and negative relationships between kdeep_br_in, kdeep_br_out, and S+Basic_pKa (Figure ). Hence, we can conclude that this hybrid model accurately simulates brain concentration-time profiles. shown in Table and Figure , which indicate that the evaluation metrics were similar to MACCS Keys (RMSE: 0.269 to 0.662 and R2-value: -0.252 to 0.422) when using ECFP4