These show that decreasing exposure by maximization of CL and minimization of VDSS, decreases the effectiveness of the drug. However, the increased exposure by minimization of CL and maximization of VDSS, does not compensate for the decrease in potency by only maximizing the A 2A R affinity. Therefore, these simulations can help in identifying the most promising drug candidates. Simulations with four selected compounds with extreme (highest or lowest elimination rate compound in the respective bottom and top 10% quantile of potency) values show that both favorable PK as well as good potency are necessary for achieving sufficient tumor inhibition (Figure ). The reason that no increased tumor inhibition is observed for the simulations with maximization of VDSS and minimization of CL is that optimization for either property also increases/decreases the other.