Maximizing the outcome of early ADMET models: strategies to win the drug-hunting battles?

Despite substantial changes in the drug discovery paradigm leveraged from the advancement of early ADMET technologies, an open debate remains on how full the return on investment is, along with where to balance risks to costs of lost opportunities in the clinic. Here, the recent advancement of ADMET tools, the areas where they seem to work and where their application and connection with physiology in man remain challenging are briefly reviewed. While the 'more is better' type of 'box-checking' profiling strategy is no longer viable, the key to success lies in an intelligent integration of existing in silico, in vitro and in vivo ADMET data to help generate and test hypotheses that are critical for projecting the benefits and risks of a drug candidate in the clinic. The improvement of in silico, in vitro and in vivo correlations (ISIVIVC) and best utilization of early ADMET data are far more critical and urgent than expanding capacity and portfolio in leveraging ADMET to win the drug-hunting battles in the post-genome era.