Subscribe: Nature Reviews Drug Discovery - Issue - science feeds
Preview: Nature Reviews Drug Discovery - Issue - science feeds

Nature Reviews Drug Discovery - Issue - science feeds


Defining the brain circuits involved in psychiatric disorders: IMI-NEWMEDS


Despite the vast amount of research on schizophrenia and depression in the past two decades, there have been few innovative drugs to treat these disorders. Precompetitive research collaborations between companies and academic groups can help tackle this innovation deficit, as illustrated by the achievements of

Alzheimer amyloid hypothesis lives on


Despite the failure of Eli Lilly's anti-amyloid antibody solanezumab in its latest phase III trial for Alzheimer disease, a bulging pipeline of amyloid-modulating candidates and novel clinical trial strategies still hold promise.

3D cell technologies head to the R&D assembly line


Organs-on-chips and organoids are set to start addressing key drug discovery bottlenecks.

R&D returns continue to fall


Big pharma's return on investment for R&D expenditure fell to 3.7% in 2016, shows an annual report from Deloitte (Fig. 1). This marks a low point since the consultants started tracking these data in 2010.The analysis tracks the R&D returns of

Cures Act shakes up the FDA and NIH


President Barack Obama signed the 312-page 21st Century Cures Actinto law, bringing sweeping changes to both the FDA and NIH.One of the broadest changes in the Act is that the FDA must work to incorporate real world data into its regulatory decision-making processes.

Trial watch: Opportunities and challenges of the 2016 target landscape


Drug discovery and development is competitive and risky, especially when it comes to choosing the right target. Researchers need to balance the scientific validity of a target with factors such as the number of other companies developing drugs for that target, the clinical stages of

Market watch: Upcoming market catalysts in Q1 2017


Potentially important market catalysts in the first quarter of 2017 include top-line phase IIb/III trial results for PRO 140 (developed by CytoDyn, Progenics Pharmaceuticals and PDL BioPharma) in highly treatment-experienced patients with HIV and top-line phase II/III trial results for CR845 (developed by Cara Therapeutics,

John Lechleiter


John Lechleiter started working at Eli Lilly in a research laboratory, as an organic chemist, in 1979. Over the next three decades, he climbed the management ladder all the way to the top, becoming Chief Executive Officer (CEO) of the large pharmaceutical company in 2008. In December, after 37 years at Lilly, Lechleiter retired. He spoke with Asher Mullard about his career path, the prospects for chemists with their eyes on the executive suite and his high-risk, high-reward bets on Alzheimer disease drug development.

Drug launch curves in the modern era


The shape of the predicted sales launch curve can dramatically affect financial models of pre-commercial drugs. This article provides an update on a commonly used framework for modelling launch curves.

Anticancer drugs: Cutting the antioxidant supply chain


The reducing agent glutathione is particularly important to cancer cells, as the expression of oncogenes and the high rates of metabolism in these cells result in the production of excessive quantities of reactive oxygen species (ROS). Cramer et al. now report a novel therapeutic

Drug delivery: Star-shaped pill sustains drug release


Long-acting sustained-release oral therapies have the potential to substantially improve patient adherence and reduce side effects. However, the development of such therapeutics is limited by a rapid gastrointestinal (GI) transit time. Now, writing in Science Translational Medicine, Traverso, Langer and colleagues report the design

Anticancer drugs: Switching off immune suppression


Two papers have shown in mouse tumour models that targeting PI3Kγ in myeloid cells can reduce immune suppression and increase the efficacy of immune checkpoint inhibitors.Kaneda et al. first examined data from The Cancer Genome Atlas on head and neck squamous cell carcinoma

Cancer: Microtubule-straightening compound widens the therapeutic window


Microtubule-targeting agents (MTAs) are standard-of care chemotherapeutics for a wide range of cancers, but their use is limited by side effects such as neuropathy. Now, reporting in Science Translational Medicine, Brouhard, Roulston and colleagues present a novel small-molecule MTA that has potent antitumour activity

Cardiovascular disease: Dietary supplement protects the heart


Ageing is typically associated with cardiac hypertrophy and decline of diastolic function. Eisenberg et al. report that dietary supplementation with the natural polyamine spermidine significantly extends the median lifespan of mice. Moreover, in aged mice, spermidine reversed age-associated hypertrophy and improved cardiac diastolic function

Antibacterials: Microcins limit intestinal infection


Small proteins known as microcins that are secreted from commensal intestinal bacteria exhibit antibacterial properties in vitro. Sassone-Corsi et al. now show in mouse colitis models, that inoculation with a probiotic microcin-secreting Escherichia coli strain (EcN) outcompetes and limits gut colonization with

Alzheimer disease: BACE1 inhibitor reduces β-amyloid production in humans


Inhibition of aspartyl protease β-site amyloid precursor protein cleaving enzyme 1 (BACE1), required for production of β-amyloid (Aβ) peptides, is an attractive approach to lower Aβ levels in AD. Kennedy et al. present verubecestat (MK-8931), the first BACE1 inhibitor to reach phase III clinical

Computational chemistry: Novel virtual screening approach


Structure-based drug discovery methods are generally based on predicting the binding affinity of a ligand to a protein. Ruiz-Carmona et al. introduce a novel computational procedure termed dynamic undocking (DUck), which evaluates the structural stability of protein–ligand complexes. DUck calculates the work needed to

Diabetes: Turning down galectin 3 to combat insulin resistance


Insulin resistance is a hallmark of type 2 diabetes and is associated with inflammation of insulin target tissues such as adipose tissue, muscle and liver. A recent study by Olefsky and colleagues has shown that galectin 3 (GAL3) provides a crucial mechanistic link between inflammation

Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targets


Mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), exist in many tissues and are known to actively migrate to sites of tissue injury, where they participate in wound repair. Tumours can be considered “wounds that never heal” and, in response to cues from

Anti-colony-stimulating factor therapies for inflammatory and autoimmune diseases


Granulocyte–macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF; also known as CSF1), granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3) can each play a part in the host response to injury and infection, and there is burgeoning interest in targeting these CSFs in inflammatory and autoimmune

Genome-wide association studies of drug response and toxicity: an opportunity for genome medicine


Genome-wide association studies (GWAS) provide an unbiased approach for the discovery of potential mechanisms and pathways that underlie human characteristics, diseases and drug responses. As common diseases are frequently associated with genetic variants that exert small effect sizes, GWAS have increasingly focused on large cohorts

A comprehensive map of molecular drug targets


The success of mechanism-based drug discovery depends on the definition of the drug target. This definition becomes even more important as we try to link drug response to genetic variation, understand stratified clinical efficacy and safety, rationalize the differences between drugs in the same therapeutic