Nature Reviews Drug Discovery
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Targeting adipose tissue in the treatment of obesity-associated diabetes

Nature Reviews Drug Discovery 15, 639 (2016). doi:10.1038/nrd.2016.75 Authors: Christine M. Kusminski, Perry E. Bickel & Philipp E. Scherer Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of (Source: Nature Reviews Drug Discovery)

2016-09-02

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

Nature Reviews Drug Discovery 15, 620 (2016). doi:10.1038/nrd.2016.89 Authors: Robert G. Gourdie, Stefanie Dimmeler & Peter Kohl Our understanding of the functions of cardiac fibroblasts has moved beyond their roles in heart structure and extracellular matrix generation and now includes their contributions to paracrine, mechanical and electrical signalling during ontogenesis and normal cardiac activity. Fibroblasts also have central roles in pathogenic remodelling (Source: Nature Reviews Drug Discovery)

2016-09-02

Twenty years on: the impact of fragments on drug discovery

Nature Reviews Drug Discovery 15, 605 (2016). doi:10.1038/nrd.2016.109 Authors: Daniel A. Erlanson, Stephen W. Fesik, Roderick E. Hubbard, Wolfgang Jahnke & Harren Jhoti After 20 years of sometimes quiet growth, fragment-based drug discovery (FBDD) has become mainstream. More than 30 drug candidates derived from fragments have entered the clinic, with two approved and several more in advanced trials. FBDD has been widely applied in both academia and industry, (Source: Nature Reviews Drug Discovery)

2016-09-02

Accelerating global innovation to address antibacterial resistance: introducing CARB-X

Nature Reviews Drug Discovery 15, 589 (2016). doi:10.1038/nrd.2016.155 Authors: Kevin Outterson, John H. Rex, Tim Jinks, Peter Jackson, John Hallinan, Steve Karp, Deborah T. Hung, Francois Franceschi, Tyler Merkeley, Christopher Houchens, Dennis M. Dixon, Michael G. Kurilla, Rosemarie Aurigemma & Joseph Larsen A global response to the chronic shortfall in antibiotic innovation is urgently needed to combat antimicrobial resistance. Here, we introduce CARB-X, a new global public–private partnership that will invest more than US$350 million in the next 5 years to accelerate the progression of a diverse (Source: Nature Reviews Drug Discovery)

2016-09-02

The bladder cancer drug market

This article analyses the late-stage pipeline for bladder cancer and the impact of new drugs in this rapidly growing market. (Source: Nature Reviews Drug Discovery)

2016-09-02

Metabolic disease: Leptin sensitizer reverses obesity

Nature Reviews Drug Discovery 15, 601 (2016). doi:10.1038/nrd.2016.166 Author: Sarah Crunkhorn Leptin is an adipocyte-derived hormone that acts on the central nervous system (CNS) to regulate appetite and body weight. Despite high levels of circulating leptin, obese patients develop central leptin resistance, and leptin therapy is therefore ineffective. Now, writing in Nature Medicine, Ozcan and (Source: Nature Reviews Drug Discovery)

2016-09-02

Cardiovascular disease: Reactivating cellular rubbish removal ameliorates atherosclerosis

Nature Reviews Drug Discovery 15, 602 (2016). doi:10.1038/nrd.2016.171 Author: Mariam Faruqi Efferocytosis, a process by which apoptotic and diseased cells are cleared by macrophages, is impaired in atherosclerosis, leading to the accumulation of diseased vascular cells and apoptotic debris within the blood vessel lumen. It has been unclear why — and how — clearance of these (Source: Nature Reviews Drug Discovery)

2016-09-02

Antibacterial drugs: Nosing around for new antibiotics

Nature Reviews Drug Discovery 15, 604 (2016). doi:10.1038/nrd.2016.170 Author: Megan Cully New antibiotics are urgently needed to address the growing problem of drug resistance. Now, Peschel and colleagues have identified an antibacterial compound — lugdunin — produced by a nasal commensal bacteria. Importantly, lugdunin has a novel chemical structure, which could provide a basis for a (Source: Nature Reviews Drug Discovery)

2016-09-02

Remyelination researchers regroup after proof-of-concept setback in multiple sclerosis

Nature Reviews Drug Discovery 15, 660 (2016). doi:10.1038/nrd.2016.172 Author: Asher Mullard Nature Reviews Drug Discovery15, 519–521 (2016)An RXRγ isoform-specific agonist was incorrectly identified as an RXRγ isoform-specific inhibitor. This has now been corrected online. (Source: Nature Reviews Drug Discovery)

2016-09-02

Pharma pumps up anti-tau Alzheimer pipeline despite first Phase III failure

Nature Reviews Drug Discovery 15, 591 (2016). doi:10.1038/nrd.2016.176 Author: Asher Mullard AbbVie, Bristol-Myers Squibb, Genentech, Janssen and Merck & Co. have all advanced anti-tau candidates into Phase I trials in the hunt for drugs that can modify the course of Alzheimer disease. (Source: Nature Reviews Drug Discovery)

2016-09-02

Sickle cell solutions in sight

Nature Reviews Drug Discovery 15, 593 (2016). doi:10.1038/nrd.2016.177 Author: Katie Kingwell New targets, new drug modalities and new business strategies are drawing long-awaited attention to sickle cell disease. (Source: Nature Reviews Drug Discovery)

2016-09-02

Leading microbiome-based therapeutic falters in Phase II trial

Nature Reviews Drug Discovery 15, 595 (2016). doi:10.1038/nrd.2016.181 Author: Asher Mullard Seres's SER-109 will miss the primary end point in its Phase II trial in patients with Clostridium difficile infection, showed an interim analysis of the trial last month. The setback highlights the uncertainty ahead for a burgeoning field of microbiome-based drugs.Faecal microbiota (Source: Nature Reviews Drug Discovery)

2016-09-02

mRNA-based drug approaches Phase I milestone

Nature Reviews Drug Discovery 15, 595 (2016). doi:10.1038/nrd.2016.182 Author: Asher Mullard Moderna and partner AstraZeneca have filed paperwork to advance the first 'secreted protein' mRNA drug into Phase I trials. Initiation of the trial will be an important test for a new drug modality that aims to selectively boost the production of proteins of interest. (Source: Nature Reviews Drug Discovery)

2016-09-02

EMA rewrites Phase I guidelines in aftermath of FAAH tragedy

Nature Reviews Drug Discovery 15, 595 (2016). doi:10.1038/nrd.2016.183 Author: Asher Mullard The European Medicines Agency (EMA) is proposing a set of changes to its guidelines on how to reduce the risks of first-in-human trials. The agency says a rewrite is needed in part to incorporate lessons learnt from the tragic Phase I first-in-human trial of (Source: Nature Reviews Drug Discovery)

2016-09-02

Trial watch: Impact of genetically supported target selection on R & D productivity

Nature Reviews Drug Discovery 15, 596 (2016). doi:10.1038/nrd.2016.164 Authors: Mark R. Hurle, Matthew R. Nelson, Pankaj Agarwal & Lon R. Cardon Various remedies have been proposed to tackle the long-standing problem of high attrition in drug development due to safety, efficacy and other causes. Occasionally, such analyses have been accompanied by quantitative evaluations of the factors involved. For example, we recently estimated that drug mechanisms with (Source: Nature Reviews Drug Discovery)

2016-09-02

Deal watch: Galderma pursues 'itchy cytokine' by licensing antibody from Roche's Chugai

Nature Reviews Drug Discovery 15, 597 (2016). doi:10.1038/nrd.2016.165 Author: Megan Cully Galderma Pharma has agreed to license nemolizumab from Chugai Pharmaceutical Co. for an undisclosed amount (Fig. 1). Nemolizumab is a humanized monoclonal antibody that targets the interleukin-31 (IL-31) receptor-α (IL-31RA) and is being developed for atopic dermatitis (eczema) and pruritus (itching). Galderma will (Source: Nature Reviews Drug Discovery)

2016-09-02

Melissa Paoloni

Nature Reviews Drug Discovery 15, 598 (2016). doi:10.1038/nrd.2016.174 When the I-SPY 2 trial was launched in 2010, it was welcomed as a first test of an adaptive trial strategy that would simultaneously collect data on multiple drugs from different pharmaceutical partners. The Phase II signal-finding trial has now enrolled more than 1,000 patients, testing 12 different experimental regimens from 9 different pharmaceutical partners in neoadjuvant breast cancer. I-SPY2 has 'graduated,' five drugs that are considered to have a high likelihood of succeeding in confirmatory Phase III trials, and last year investigators amended its protocol so that it can run indefinitely. For , director of advanced trials at QuantumLeap Healthcare Collaborative, the charity that is sponsori...

2016-09-02

Receptor pharmacology: The many faces of G protein-coupled receptors

Nature Reviews Drug Discovery 15, 602 (2016). doi:10.1038/nrd.2016.179 Author: Katie Kingwell The ability of different agonists to activate different signalling pathways from a G protein-coupled receptor (GPCR), despite binding the same receptor pocket, is a well-known phenomenon, but the underlying mechanisms have not been clear. Now, Lefkowitz and colleagues have used single-domain antibodies (nanobodies) to probe (Source: Nature Reviews Drug Discovery)

2016-09-02

Autoimmune diseases: CAR-T cells take aim at autoimmunity

Nature Reviews Drug Discovery 15, 603 (2016). doi:10.1038/nrd.2016.180 Author: Alexandra Flemming Current treatments for autoimmune diseases mostly rely on general immunosuppression, leaving patients prone to infections. Approaches that specifically target pathogenic autoimmune cells in autoimmune diseases would be ideal; however, strategies to achieve this have so far been elusive. Now, reporting in Science, Ellebrecht et (Source: Nature Reviews Drug Discovery)

2016-09-02

Ageing: Improving muscle function

Nature Reviews Drug Discovery 15, 604 (2016). doi:10.1038/nrd.2016.167 Author: Sarah Crunkhorn The biological effects of urolithins (metabolites of ellagitannins, which are found in pomegranates, nuts and berries) are poorly characterized. Here, Ryu and colleagues report that urolithin A (UA) extends lifespan and improves fitness of Caenorhabditis elegans. These effects were mediated by the induction of (Source: Nature Reviews Drug Discovery)

2016-09-02
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