First, we generated novel A 2A R inhibitors using the multi-objective de novo drug design framework DrugEx 17 with QSPR models for target affinity and for each PK property (CL, VDSS, FU). The optimization criteria here were to either maximize or minimize the respective PK property in addition to maximization of the affinity. While this does not directly reflect the optimization criteria during drug discovery/development, it allows us to analyze the effect of the optimization for certain PK properties in isolation, e.g. through comparison with high/low PK value compounds in the dataset. Finally, we compared predicted tumor inhibition using an A 2A R QSP model for molecules generated with only target affinity as optimization criteria versus molecules generated with PK and target affinity as criteria. Figure shows a graphical representation of the proposed workflow.