To interpret the estimated substructures, we selected drugs whose suggested important substructures either agreed or disagreed with the knowledge of medicinal chemistry. We (Ouabain), respectively. Hence, we conclude that each substructure contributes substantially to the decrease in lipophilicity compared to its entire structure, which can worsen membrane permeability. The substructures for case E are shown in Figure . These two examples are not consistent with the results published in previous reports. For example, tetrahydro-2H-pyran-2,3,5-triol (cLogP: -1.2 and PSA:69.9) was suggested as an important substructure in Gentamicin (cLogP: -4.2 and PSA:199.7). A low permeability of gentamicin has also been reported . Although we can barely interpret that several hydroxyl groups (H-bond donors) of this substructure contributed to the decrease in lipophilicity and could lead to the worsening of membrane permeability, several amine groups, which were not included in the suggested substructure, were considered to contribute to the decrease in lipophilicity rather than the hydroxyl group. Another example is N-benzylnaphthalen-1-amine (cLogP: -2.9 and PSA:562.7), which was suggested as an important substructure in suramin (cLogP:3.9 and PSA:12.0).