and mouse ADORA3 performed well with coefficient of determination R 2 between 0.6 and 0.7 during cross-validation (Figure ). Surprisingly human ADORA1, ADORA2a, mouse ADORA3 and bovine ADORA1 performed quite bad with median R 2 lower than 0.5 with fold performance reaching -2.3 to -2.1 for the first three. Nonetheless, the maximum error associated with these first three was significantly lower than that of other QSAR models although the root-mean-square error (RMSE) and mean absolute error (MAE) of all models were not significantly different. With regards to external validation (Figure ), the performance of the predictions on the temporally split test set performed as expected with RMSE around 1 log unit for most models, only human ADORA1 and mouse ADORA3 performing noticeably badly. The PCM regression model performed quite well at cross-validation in terms of R and RMSE with values of 0.59 and 0.72 but had higher median maximum error than all QSAR models. These results