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Katz and colleagues summarize knowledge on associations between drug pharmacokinetics and variations in genes coding for proteins involved in drug disposition. They propose a novel strategy in which pharmacogenetic data from early clinical studies is used both to feed back to furtherin vitrostudies of drug pharmacokinetics and to feed forward to optimize later-stage clinical trials, and discuss how this could improve drug development.
The melanocortin system is a central element in the control of energy homeostasis, sexual behaviour and autonomic functions. Here, Wikberg and Mutulis discuss the potential of targeting melanocortin receptors across multiple therapeutic areas, and highlight opportunities and challenges for drug discovery in the melanocortin pathway.
In recent years, the prevalence of multidrug-resistant bacteria has grown considerably, exacerbated by the limited discovery of novel classes of antibacterial agents. Here, Lock and Harry discuss the therapeutic potential of inhibiting bacterial cell division, highlight specific cell-division proteins representing likely antimicrobial targets, and review the recent progress in this exciting new field.
Understanding of the functional significance of the wide structural diversity of G-protein-coupled receptors (GPCRs) — one of the most important families of drug targets — has advanced considerably in recent years. This article provides a comprehensive overview of the five main human GPCR families, discussing gene repertoire, general ligand preference, common and unique structural features, and the potential for future drug discovery.
Ion channels remain an under-exploited drug target class owing to the low-throughput nature of patch-clamp electrophysiology. In this Review, Dunlop and colleagues evaluate automated electrophysiology platforms and discuss their impact in terms of ion-channel screening, lead optimization and the assessment of cardiac ion-channel safety liability.
