Nature Reviews Drug Discovery contents April 2015 Volume 14 Number 4 pp 221-294

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TABLE OF CONTENTS
April 2015 Volume 14 Number 4		Advertisement
Impact Factor 37.231 *	In this issue Comment News and Analysis Research Highlights Perspectives Reviews Correspondence Also this month Article series: A guide to drug discovery  Featured article: Mitigating risk in academic preclinical drug discovery Jayme L. Dahlin, James Inglese & Michael A. Walters	Protein expression & purification—learn practical production tips from experts A centralized place to expand your knowledge on every step of protein expression and purification. Get free access NOW
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Animation: Targeting cancer cell metabolism This animation, created by Nature Reviews Drug Discovery, with distribution supported by Forma Therapeutics, explores the key aspects of the altered metabolism in cancer cells and explains how these can be exploited for the development of new anticancer strategies.  Access the animation free online.  Produced with support from: Forma Therapeutics, Inc.
Comment: The European Medicines Agency's strategies to meet the challenges of Alzheimer disease Manuel Haas, Valentina Mantua, Marion Haberkamp, Luca Pani, Maria Isaac, Florence Butlen-Ducuing, Spiros Vamvakas & Karl Broich p221 | doi:10.1038/nrd4585 Regulatory agencies have a key role in facilitating the development of new drugs for Alzheimer disease, particularly given the challenges associated with early intervention. Here, we summarize the strategies of the European Medicines Agency to help address such challenges. Abstract | Full Text | PDF
NEWS AND ANALYSIS		Top
The Roadmap Epigenomics Project opens new drug development avenues Asher Mullard p223 | doi:10.1038/nrd4582 The US National Institutes of Health's US$240-million epigenomics investment could improve the study of disease biology, the identification of new drug targets, the validation of animal models and more. PDF
HDAC inhibitors still need a home run, despite recent approval Malini Guha p225 | doi:10.1038/nrd4583 A beleaguered class of epigenetic modulators continues to struggle for oncology success, but new insights into their mechanisms in cancer may yet offer hope. PDF
NEWS IN BRIEF AbbVie pays $21 billion for Pharmacyclics' BTK inhibitor Asher Mullard p227 | doi:10.1038/nrd4605 PDF
Industry head-to-head trials favour sponsor Asher Mullard p227 | doi:10.1038/nrd4606 PDF
Oral GLP1 analogue rounds Phase II corner Asher Mullard p227 | doi:10.1038/nrd4607 PDF
BIOBUSINESS BRIEFS Market watch: Upcoming catalysts in Q2 2015 Justin Burns p228 | doi:10.1038/nrd4598 PDF
BIOBUSINESS BRIEFS Trial watch: Multikinase-targeting therapy finds potential niche in thyroid cancer Megan Cully p229 | doi:10.1038/nrd4599 PDF
AN AUDIENCE WITH Eric Karran p230 | doi:10.1038/nrd4584 Eric Karran, Director of Research at Alzheimer's Research UK, discusses his plan to shore up the Alzheimer's disease pipeline. PDF
FROM THE ANALYST'S COUCH The breast cancer market Basharut A. Syed p233 | doi:10.1038/nrd4571 Several new drugs have recently been approved for the treatment of breast cancer, and this analysis provides a market outlook as well as an insight into the pipeline of agents in late-stage development. PDF
RESEARCH HIGHLIGHTS Top Anticancer drugs: On-site CAR parking p235 | doi:10.1038/nrd4586 PDF Muscular dystrophy: New exon-skipping strategy rescues dystrophin p236 | doi:10.1038/nrd4587 PDF Cancer: An epigenetic target for synthetic lethality p236 | doi:10.1038/nrd4589 PDF Inflammatory diseases: Starving inflammation p237 | doi:10.1038/nrd4590 PDF Parasite infection: Parasite-targeting compound sets identified and ready to go p238 | doi:10.1038/nrd4588 PDF IN BRIEF Metabolic disease: Novel decretin hormone identified | Infectious disease: Towards an effective HIV vaccine | Tuberculosis: Improving drug delivery | Pain: Predicting clinical efficacy PDF Drug Discovery JOBS of the week Computational and Systems Biology of Pathogen Drug Resistance University of Notre Dame Post-Doctoral Position-Neuroscience (drug discovery) The Scripps Research Institute - Florida Research Laboratory Head Pharmacology / Oncology Drug Discovery (m / f) Boehringer Ingelheim Postdoctoral Fellow in CNS and / or Bone Drug Delivery, Texas, USA Texas Tech University Health Sciences Center Drug Development for Anemia Lund University More Science jobs from Drug Discovery EVENT Learning from Cancer to Advance Neurodegeneration Drug Discovery and Development 11.06.15 New York, USA More science events from
PERSPECTIVES		Top
OPINION A holistic approach to targeting disease with polymeric nanoparticles Christopher J. Cheng, Gregory T. Tietjen, Jennifer K. Saucier-Sawyer & W. Mark Saltzman p239 | doi:10.1038/nrd4503 Drug delivery methods that use targeted polymeric nanoparticles have the potential to increase local concentrations of a drug while reducing off-target accumulation. To best achieve this goal, Saltzman and colleagues argue that a holistic approach should be taken, in which anatomical, molecular and temporal aspects of the nanoparticle, drug and disease are taken into consideration. Abstract | Full Text | PDF
INNOVATION Organs-on-chips at the frontiers of drug discovery Eric W. Esch, Anthony Bahinski & Dongeun Huh p248 | doi:10.1038/nrd4539 Microengineered cell culture systems are becoming sufficiently sophisticated that they can recapitulate many of the phenomena observed in tissues and organisms. Here, Huh and colleagues discuss the advances made in these 'organs-on-chips' and how they could be used in drug development, including target identification and validation, toxicity screening and stratified medicine. Abstract | Full Text | PDF
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Droplet Digital™ PCR (ddPCR™) is leading the way Last year more than 150 peer-reviewed publications took advantage of Droplet Digital PCR's unmatched ability to detect rare nucleic acid species. From tracking cancer biomarkers to quantifying rare mutations, gene expression, and miniscule viral loads, Droplet Digital PCR led to more discoveries than any other digital PCR platform. Visit our ddPCR page for application guides, publication lists, and webinars that explore the world of ddPCR.
REVIEWS		Top
Targeting the translation machinery in cancer Mamatha Bhat et al. p261 | doi:10.1038/nrd4505 Dysregulation of mRNA translation is a frequent occurrence in cancer cells, and several components of the translation machinery have emerged as promising targets for anticancer therapeutics. This Review discusses the mechanisms of aberrant mRNA translation in cancer cells and provides an overview of drugs in development that target the translation machinery. Abstract | Full Text | PDF | Supplementary information
Article series: A guide to drug discovery Mitigating risk in academic preclinical drug discovery Jayme L. Dahlin, James Inglese & Michael A. Walters p279 | doi:10.1038/nrd4578 The recent growth in the number of academic drug discovery centres is providing new opportunities to couple the curiosity-driven research culture in academia with rigorous preclinical drug discovery practices used in industry. To realize the potential of these opportunities, it is important that academic researchers understand the risks in several key areas — including organization, target selection, assay design, medicinal chemistry and preclinical pharmacology — which are discussed in this article. Abstract | Full Text | PDF | Supplementary information
CORRESPONDENCE		Top
Correspondence: Secondary pharmacology data to assess potential off-target activity of new drugs: a regulatory perspective Thomas Papoian, Haw-Jyh Chiu, Ikram Elayan, Gowraganahalli Jagadeesh, Imran Khan, Adebayo A. Laniyonu, Cindy Xinguang Li, Muriel Saulnier, Natalie Simpson & Baichun Yang p294 | doi:10.1038/nrd3845-c1 Full Text | PDF
Correspondence: Sharing pharma compounds with academia: experiences with providing vitamin D receptor ligands Arndt A. Schmitz, Sandra Hackethal, Anke Schulz, Ekkehard May, Andreas Steinmeyer, Ulrich Zügel & Khusru Asadullah p294 | doi:10.1038/nrd4008-c1 Full Text | PDF
Erratum: Advances in the development of influenza virus vaccines Florian Krammer & Peter Palese p294 | doi:10.1038/nrd4595 Full Text | PDF
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*2013 Journal Citation Report (Thomson Reuters, 2014)

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