Learning from the 2012-2013 class of breakthrough therapies doi:10.1038/nrd4196 The expedited US regulatory pathway for 'breakthrough therapies' has already yielded its first two approvals and more than 26 designations, for 30 candidates in 22 indications. Full Text
The GHIT fund shows its cards doi:10.1038/nrd4197 Japan's biggest pharmaceutical companies, the Bill and Melinda Gates Foundation, and the Japanese government have awarded their first round of global health research grants. Full Text
Market watch: Defining and quantifying the use of personalized medicines doi:10.1038/nrd4177 The authors propose a definition for personalized medicines and provide an objective and longitudinal quantification of worldwide use of personalized medicines, which could serve as a baseline from which to measure their future uptake. Full Text
Trial watch: Phase II boost for glutamate-targeted antidepressants doi:10.1038/nrd4178 The results of a Phase II trial suggest that the ketamine-like drug lanicemine has a sustained antidepressant effect without the acute psychosis-like side effects of ketamine. Full Text
Glucokinase alternative doi:10.1038/scibx.2013.1279 Compounds that directly activate glucokinase effectively reduce blood sugar in patients with diabetes but increase the risk of adverse hypoglycemic events. Now, researchers from Amgen have identified compounds that act via a glucokinase regulator, opening the door to a potentially safer strategy to modulate hepatic glucokinase activity. Full Text
Does size matter in R&D productivity? If not, what does? doi:10.1038/nrd4164 This analysis of factors that affect the likelihood of success in drug research and development (R&D) indicates that scientific acumen and good judgment – particularly with regard to the early termination of less viable drug candidates – are crucial. Full Text
Autoimmune disease: Parkinson's drug promotes myelin repair doi:10.1038/nrd4181 A study in Nature reports that a drug currently approved for the treatment of Parkinson's disease promotes neuronal myelination and decreases the clinical severity of MS in mouse models. Full Text
Neurological disorders: Chloride extrusion alleviates neuropathic pain doi:10.1038/nrd4183 Activators of the potassium-chloride co-transporter KCC2 show promising oral efficacy in a rat model of neuropathic pain. Full Text
Bone disorders: Targeting NOX4 knocks down osteoporosis doi:10.1038/nrd4182 NADPH oxidase 4 (NOX4) – an enzyme that is involved in the production of reactive oxygen species – could be a therapeutic target for disorders characterized by bone loss, such as osteoporosis. Full Text
Modulation of oxidative stress as an anticancer strategy doi:10.1038/nrd4002 The role of ROS in cancer cells is controversial as they can have both pro-tumorigenic and antitumorigenic properties. This article discusses recent findings that cancer cells upregulate antioxidant pathways to counteract ROS, and explores the potential of anticancer strategies that target the antioxidant capacity of tumour cells. Full Text
Chemical predictive modelling to improve compound quality doi:10.1038/nrd4128 The potency, selectivity and pharmacokinetic characteristics of small-molecule compounds are some of the key factors influencing their chances of success in clinical trials. This article discusses the application of computational methods, particularly quantitative structure-activity relationships, in guiding the selection of higher-quality drug candidates. Full Text
bHLH–PAS proteins in cancer doi:10.1038/nrc3621 Mammalian basic HLH (helix-loop-helix)-PER-ARNT-SIM (bHLH-PAS) proteins are heterodimeric transcription factors. Recently determined structures of their PAS domains and successful small-molecule screening programmes are now providing new opportunities to discover selective agonists and antagonists directed against this multitasking family of transcription factors. Full Text
Antimalarial drug discovery – approaches and progress towards new medicines doi:10.1038/nrmicro3138 Current antimalarial therapy heavily relies on artemisinins, a drug class that only targets the blood stages of the parasite and which is increasingly feared to elicit drug resistance. This article discusses the approaches used to develop novel drugs that are active against different life cycle stages with the ultimate aim of eliminating malaria. Full Text
Career snapshots archive Career snapshots feature people associated with drug discovery and drug development, with the aim of providing expert insights and advice on a wide range of positions and career paths in this field. Full Text
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