Nature Reviews Drug Discovery contents December 2017 Volume 16 Number 12 pp 811-883

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TABLE OF CONTENTS
December 2017 Volume 16 Number 12		Advertisement
2016 2-year Impact Factor 57.000 Journal Metrics 2-year Median 38	In this issue Comment News and Analysis Research Highlights Analysis Reviews   Also this month  Featured article: Tau-based therapies in neurodegeneration: opportunities and challenges Chuanzhou Li & Jürgen Götz	Do you have novel targets for collaborative drug discovery? We could award your lab £100,000 Our translational awards will be made to the PI after the successful review of the project and feasibility in our drug discovery labs. Collaborate with LifeArc, the charity turning great science into greater patient impact. Visit https://www.lifearc.org/working-with-us/drug-discovery/
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Nature Outline: Fatty liver disease  The worldwide rise in obesity and diabetes has led to a spike in the incidence of non-alcoholic fatty liver disease, which often progresses to the more severe non-alcoholic steatohepatitis. This Outline discusses diagnostic techniques and therapies.  Access the Outline free online  Produced with support from:  Gilead Sciences
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Comment: Legacy data sharing to improve drug safety assessment: the eTOX project Ferran Sanz, François Pognan, Thomas Steger-Hartmann, Carlos Díaz, Montserrat Cases, Manuel Pastor, Philippe Marc, Joerg Wichard, Katharine Briggs, David K. Watson, Thomas Kleinöder, Chihae Yang, Alexander Amberg, Maria Beaumont, Anthony J. Brookes, Søren Brunak, Mark T. D. Cronin, Gerhard F. Ecker, Sylvia Escher, Nigel Greene, Antonio Guzmán, Anne Hersey, Pascale Jacques, Lieve Lammens, Jordi Mestres, Wolfgang Muster, Helle Northeved, Marc Pinches, Javier Saiz, Nicolas Sajot, Alfonso Valencia, Johan van der Lei, Nico P. E. Vermeulen, Esther Vock, Gerhard Wolber & Ismael Zamora p811 | doi:10.1038/nrd.2017.177 The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through the Innovative Medicines Initiative to explore this possibility. Abstract | Full Text | PDF | Supplementary information
NEWS AND ANALYSIS		Top
Small molecules against RNA targets attract big backers Asher Mullard p813 | doi:10.1038/nrd.2017.239 Novartis, Merck, Pfizer and biotech entrepreneurs have started working on small-molecule drugs that act on an assortment of RNA targets, hoping to unlock once undruggable targets and new biology. PDF
Cryo-electron microscopy makes waves in pharma labs Mark Peplow p815 | doi:10.1038/nrd.2017.240 Companies hope the Nobel Prize-winning imaging methodology will reveal biomolecule characteristics that can guide drug discovery projects. PDF
NEWS IN BRIEF FDA approves first digital pill Asher Mullard p818 | doi:10.1038/nrd.2017.248 PDF
Second anticancer CAR T therapy receives FDA approval Asher Mullard p818 | doi:10.1038/nrd.2017.249 PDF
BTK inhibitors get a boost Asher Mullard p818 | doi:10.1038/nrd.2017.250 PDF
BIOBUSINESS BRIEFS Trial watch: Tracing investment in drug development for Alzheimer disease Alpha Tom Kodamullil, Firas Zekri, Meemansa Sood, Bastian Hengerer, Luc Canard, Duncan McHale & Martin Hofmann-Apitius p819 | doi:10.1038/nrd.2017.169 PDF
AN AUDIENCE WITH Eric Rubin p820 | doi:10.1038/nrd.2017.228 Eric Rubin, vice president of clinical oncology at Merck & Co, discusses tumour-agnostic approvals, immunotherapy combinations and the modernization of clinical trial eligibility criteria. PDF
FROM THE ANALYST'S COUCH The human microbiome: opportunity or hype? Pedro M. Valencia, Magali Richard, Jesse Brock & Elsy Boglioli p823 | doi:10.1038/nrd.2017.154 This article discusses investment in microbiome-based therapeutic approaches and key questions for the field related to the underlying science, clinical development, regulation and business models. PDF
RESEARCH HIGHLIGHTS   Top Sepsis: Stalking a new target p825 | doi:10.1038/nrd.2017.238 PDF Metabolic disease: Ectopic olfactory receptor activation reverses obesity p826 | doi:10.1038/nrd.2017.230 PDF Cancer: Bispecific antibody directs T cells to solid tumours p826 | doi:10.1038/nrd.2017.237 PDF Obesity: GDF15 tells the brain to lose weight p827 | doi:10.1038/nrd.2017.241 PDF Cancer immunotherapy: Rewiring cancer cells p828 | doi:10.1038/nrd.2017.242 PDF   IN BRIEF Polypharmacology: Repurposing ceritinib | Infectious disease: Fighting influenza B | Diabetes: Selective FOXO1 modulation | GPCRs: Crystal structure of D4 dopamine receptor PDF Drug Discovery JOBS of the week Principal Scientist in Cellular Pharmacology Johnson & Johnson MRC WIMM Prize PhD Studentships Weatherall Institute of Molecular Medicine, University of Oxford Postdoctoral, Department of Pharmaceutical Sciences State University of New York Tenured Professor Position UNIVERSITY OF ILLINOIS AT CHICAGO- College of Medicine Postdoctoral Fellow Washington University School of Medicine, St. Louis More Science jobs from Drug Discovery EVENT 20th Annual Superbugs & Superdrugs 19.03.18 London, UK More science events from
ANALYSIS		Top
Trends in GPCR drug discovery: new agents, targets and indications Alexander S. Hauser, Misty M. Attwood, Mathias Rask-Andersen, Helgi B. Schiöth & David E. Gloriam p829 | doi:10.1038/nrd.2017.178 G protein-coupled receptors (GPCRs) are the most intensively studied class of drug targets. This article presents a pioneering analysis of all GPCR-targeted drugs and agents that are currently in clinical trials, and discusses the trends across molecule types, drug targets and therapeutic indications. Abstract | Full Text | PDF
REVIEWS		Top
JAK inhibition as a therapeutic strategy for immune and inflammatory diseases Daniella M. Schwartz, Yuka Kanno, Alejandro Villarino, Michael Ward, Massimo Gadina & John J. O'Shea p843 | doi:10.1038/nrd.2017.201 Janus kinases (JAKs) are essential signalling mediators downstream of many pro-inflammatory cytokines. Jakinibs — small-molecule inhibitors of JAKs — have gained traction as safe and efficacious options for the treatment of inflammation-driven pathologies. This Review discusses the biology, development and efficacy of jakinibs in the treatment of immune and inflammatory diseases. Abstract | Full Text | PDF
Tau-based therapies in neurodegeneration: opportunities and challenges Chuanzhou Li & Jurgen Gotz p863 | doi:10.1038/nrd.2017.155 Aggregates of the microtubule-associated protein tau are a defining feature of several neurodegenerative disorders, including Alzheimer disease (AD). Given the recent failures of several amyloid-β-targeted therapies for AD, interest is growing in tau as an alternative target, and this Review describes preclinical and clinical studies of tau-based approaches in the light of recent advances in the understanding of the physiological and pathological roles of tau. Abstract | Full Text | PDF
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Poster on: The expanding CRISPR toolbox  The CRISPR-Cas9 system can do a lot more than gene editing. This Poster, from Nature Methods, explores the newest possibilities of CRISPR. Available to download free online Produced with support from:  Dharmacon
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