Keeping vigilant about drug safety | PDF (443 KB)

p855 | doi:10.1038/nrd2455

Cancer: Multiple targets to tackle tough tumours | PDF (296 KB)

p867 | doi:10.1038/nrd2449

Inflammatory disorders: Chronically amplifying disease | PDF (195 KB)

p868 | doi:10.1038/nrd2450

Bone diseases: Central control | PDF (118 KB)

p868 | doi:10.1038/nrd2453

Anticancer drugs: Turning cancer off | PDF (356 KB)

p869 | doi:10.1038/nrd2451

Antipsychotics: An emerging alternative | PDF (206 KB)

p870 | doi:10.1038/nrd2452

The influence of drug-like concepts on decision-making in medicinal chemistry

Paul D. Leeson & Brian Springthorpe

p881 | doi:10.1038/nrd2445

Despite the wide acceptance of drug-like principles such as the 'rule of five', this analysis of molecules currently being synthesized in leading pharmaceutical companies reveals that their physical properties differ significantly from those of recently discovered oral drugs. The marked increase in lipophilicity in particular could increase the likelihood of attrition in drug development.

• Abstract
• Full Text
• PDF (541 KB)
• Supplementary information

Target deconvolution strategies in drug discovery

Georg C. Terstappen, Christina Schlüpen, Roberto Raggiaschi & Giovanni Gaviraghi

p891 | doi:10.1038/nrd2410

Target-based drug discovery has not been as successful as was hoped, in part owing to the complexities of biological systems and disease pathophysiology. This Review explores experimental strategies for the retrospective identification of molecular targets that underlie phenotypic drug effects (target deconvolution) — strategies that might be used to aid efficient drug development.

• Abstract
• Full Text
• PDF (995 KB)

Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges

Russell A. Wilke, Debbie W. Lin, Dan M. Roden, Paul B. Watkins, David Flockhart, Issam Zineh, Kathleen M. Giacomini & Ronald M. Krauss

p904 | doi:10.1038/nrd2423

Genetic factors may underlie susceptibility to serious adverse drug reactions (SADRs). Here, the authors discuss three SADRs — liver injury, myotoxicity and long QT syndrome — and consider the challenges that need to be overcome to identify predisposing genotypes, which might improve patient management.

• Abstract
• Full Text
• PDF (810 KB)

Hydrogen sulphide and its therapeutic potential

Csaba Szabó

p917 | doi:10.1038/nrd2425

Hydrogen sulphide (H₂S) is increasingly being recognized as an important signalling molecule in the cardiovascular and nervous systems. This article overviews the physiology and biochemistry of H₂S, summarizes the effects of H₂S inhibitors or H₂S donors in animal models of disease and discusses the likely options and paths for the therapeutic exploitation of H₂S.

• Abstract
• Full Text
• PDF (668 KB)
• Supplementary information

Drug safety

p937 | doi:10.1038/nrd2461

• Abstract
• Full Text
• PDF (171 KB)