The theme "New Approaches for Studying Drug and Toxicant Action: Applications to Drug Discovery and Development" links 13 articles in this volume of the Annual Review of Pharmacology and Toxicology (ARPT ). The engaging prefatory articles by Arthur Cho and Robert Lefkowitz set the stage for this theme and for the reviews that insightfully describe new approaches that advance research and discovery in pharmacology and toxicology. Examples include the progress being made in developing Organson-Chips/microphysiological systems and human induced pluripotent stem cell-derived cells to aid in understanding cell and tissue pharmacokinetics, action, and toxicity; the recognition of the importance of circadian rhythm, the microbiome, and epigenetics in drug and toxicant responses; and the application of results from new types of patient-derived information to create personalized/precision medicine, including therapeutics for pain, which may perhaps provide help in dealing with the opioid epidemic in the United States. Such new information energizes discovery efforts in pharmacology and toxicology that seek to improve the efficacy and safety of drugs in patients and to minimize the consequences of exposure to toxins. Applications to Drug Discovery and Development," complements and extends the themes of previous volumes ("Precision Medicine and Prediction in Pharmacology" and "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology"). We believe that this theme will inform readers of findings that have and will continue to have an important impact on pharmacology and toxicology. Below, we highlight 13 articles for the current theme. The highly engaging prefatory articles by Arthur Cho (the previous Editor of ARPT; 1) and Robert Lefkowitz (2) demonstrate their originality in approaching scientific discovery, although in the case of Lefkowitz, this occurred in a rather serendipitous manner. His contributions have been widely recognized, including by the 2012 Nobel Prize in Chemistry. Of note, Lefkowitz's early contributions derive from the use of radioligand binding to identify adrenergic receptors, studies that complement the early work of Solomon Snyder, whose prefatory article appeared in Volume 57 of ARPT (3). Almost 50 years after being introduced and validated as a technique, radioligand binding remains useful for characterizing drug and hormone receptors and defining aspects of receptor biology, including the identification of allosteric modulators, an active area of research and discovery in academia and the drug industry (4, 5).Radioligand binding is a reductionist approach that complements assessments of drug and toxicant responses in physiologic systems, such as organ baths. Recent progress in efforts to create ex vivo models of tissues and organs have involved the use of tissue-derived cells and cell lines that can be assembled in a manner that mimics the in vivo setting. Such microphysiological systems can create Organs-on-Chips and provide novel ways to assess pharmacokinetics, pharm...
