Chemical predictive modelling to improve compound quality 论文

摘要

The 'quality' of small-molecule drug candidates — encompassing aspects including their potency, selectivity and pharmacokinetic characteristics — is a key factor influencing the chances of success in clinical trials. Cumming and colleagues discuss the application of computational methods, particularly quantitative structure–activity relationships, in guiding the selection of higher-quality drug candidates, as well as cultural factors that may have affected their impact. The 'quality' of small-molecule drug candidates, encompassing aspects including their potency, selectivity and ADMET (absorption, distribution, metabolism, excretion and toxicity) characteristics, is a key factor influencing the chances of success in clinical trials. Importantly, such characteristics are under the control of chemists during the identification and optimization of lead compounds. Here, we discuss the application of computational methods, particularly quantitative structure–activity relationships (QSARs), in guiding the selection of higher-quality drug candidates, as well as cultural factors that may have affected their use and impact.