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Several changes to scientific culture and policy are needed to aid the identification of new drug targets and therapies for central nervous system disorders from the rapidly growing volume of 'big' data in neuroscience.
Thrombotic events are a major complication of cardiovascular disease. Despite the availability of a large range of antithrombotic therapies, demand persists for safe, effective new drugs and antidotes that allow control of their activity. This article investigates the antithrombotic drug pipeline and the changing landscape of the antithrombotics market.
Previous analyses of new drug approvals have suggested that phenotypic screening strategies have been more productive than target-based approaches in the discovery of first-in-class small-molecule drugs. Eder and colleagues analysed the origins of the first-in-class drugs approved by the US Food and Drug Administration from 1999 to 2013, and found that target-based approaches have had a substantial impact in more recent years. They discuss the implications for drug discovery strategies, including viewing phenotypic screening as a novel discipline rather than as a neoclassical approach.
There has been a resurgence of interest in the use of phenotypic screens in drug discovery as an alternative to target-focused approaches. Moffat and colleagues investigated the contribution of phenotypic assays in oncology by analysing the origins of the new small-molecule cancer drugs approved by the US Food and Drug Administration over the past 15 years. They also discuss technical and biological advances that could empower phenotypic drug discovery in oncology by enabling the development of mechanistically informed phenotypic screens.
Semaphorins — a group of cell-surface and secreted proteins whose effects are mediated by plexin receptors — are involved in intercellular communication in the nervous system, the immune system and during angiogenesis. Worzfeld and Offermanns summarize the pathological roles of semaphorins and plexins in cancer, bone diseases, immuno-inflammatory diseases and spinal cord injury, and discuss emerging strategies to therapeutically target these molecules.
MicroRNAs (miRNAs) — 21- to 23-nucleotide single-stranded RNAs that regulate gene expression — have roles in numerous diseases, and are therefore attractive therapeutic targets. Li and Rana discuss strategies in the design of miRNA-targeting oligonucleotides with increased efficacy and improvedin vivodelivery characteristics, and highlight some of the challenges that lie ahead in the clinical development of these therapeutics.
