Nature Reviews Drug Discovery contents July 2015 Volume 14 Number 7 pp 443-510

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TABLE OF CONTENTS
July 2015 Volume 14 Number 7
Impact Factor 41.908 *	In this issue Comment News and Analysis Research Highlights Perspectives Analysis Reviews Correspondence Also this month Article series: Cancer immunotherapy  Featured article: The pharmacology of second-generation chimeric antigen receptors Sjoukje J. C. van der Stegen, Mohamad Hamieh & Michel Sadelain
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Nature Immunology Focus on The immunology of HIV Nature Immunology presents a series of specially commissioned articles that discuss the most recent progress in understanding the immune response to HIV and how this new insight can be harnessed for prophylactic vaccines and immunotherapies.  Click here for more information.
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Nature Collection: Cancer immunotherapy Cancer immunotherapy is a rapidly advancing field with relevance for an expanding list of tumour types. In this collection, Nature presents seven recent articles on cancer immunotherapy.  Access the Collection free online for six months. Produced with support from:  Genentech, A Member of the Roche Group
Comment: Assessing the relative efficacy of new drugs: an emerging opportunity Hans-Georg Eichler, Andrew Thomson, Irmgard Eichler & Sebastian Schneeweiss p443 | doi:10.1038/nrd4664 The increasing availability of individual-level data from clinical trials could allow the relative efficacy of new drugs to be assessed in a robust, cost-effective and timely way. Abstract | Full Text | PDF | Supplementary information
NEWS AND ANALYSIS		Top
A β-lactamase inhibitor revival provides new hope for old antibiotics Ken Garber p445 | doi:10.1038/nrd4666 Novel inhibitors of bacterial β-lactamases should restore activity to old antibiotics and hold back the tide of drug-resistant infections. PDF
The NASH drug dash Kelly Rae Chi p447 | doi:10.1038/nrd4667 Intercept Pharmaceuticals has announced plans for the first ever pivotal trial in non-alcoholic steatohepatitis (NASH), setting a high bar for a growing pipeline of drugs against the liver disease. PDF
NEWS IN BRIEF Should the FDA disclose complete response letters? Asher Mullard p449 | doi:10.1038/nrd4686 PDF
Robust biotech sector increases R&D spend Asher Mullard p449 | doi:10.1038/nrd4687 PDF
FDA approves two IBS drugs Asher Mullard p449 | doi:10.1038/nrd4688 PDF
BIOBUSINESS BRIEFS Regulatory watch: Why do oncology drugs fail to gain US regulatory approval? Sean Khozin, Ke Liu, Jonathan P. Jarow & Richard Pazdur p450 | doi:10.1038/nrd4651 PDF
BIOBUSINESS BRIEFS Market watch: Upcoming market catalysts in Q3 2015 Clara Tan p451 | doi:10.1038/nrd4668 PDF
AN AUDIENCE WITH Moncef Slaoui p452 | doi:10.1038/nrd4669 Moncef Slaoui, Chairman of Vaccines at GlaxoSmithKline, discusses the GSK-Novartis asset swap, the future of vaccines at GSK, and the implications for the company's remaining oncology programmes. PDF
FROM THE ANALYST'S COUCH Improving R&D productivity Katarzyna Smietana, Leeland Ekstrom, Barbara Jeffery & Martin Moller p455 | doi:10.1038/nrd4650 Using a novel metric that links investment in drug research and development (R&D) to output in terms of revenue from the resultant drugs, this article analyses trends in R&D productivity overall and in specific therapeutic areas, and discusses strategies for improvement. PDF
RESEARCH HIGHLIGHTS Top Rational drug design: Tuning kinase inhibitor residence time p457 | doi:10.1038/nrd4673 PDF Obesity: Reversing resistance to leptin in obesity p458 | doi:10.1038/nrd4671 PDF Cancer: LOX does some prepping p458 | doi:10.1038/nrd4674 PDF Anticancer drugs: Selectively targeting proteins for degradation p459 | doi:10.1038/nrd4670 PDF Fibrotic diseases: New tools to target an elusive integrin p460 | doi:10.1038/nrd4672 PDF IN BRIEF Chronic kidney disease: Targeting dynamin oligomerization | Asthma: DNAzyme attenuates allergic asthma | Infectious disease: Fragment screening identifies novel HIV-1 RT inhibitors | Autoimmune disease: SIRT1 inhibition suppresses multiple sclerosis PDF Drug Discovery JOBS of the week Computational Chemist (m / f) Boehringer Ingelheim Postdoctoral Research Fellow Mayo Clinic - Rochester Assistant / Associate Professor Faculty Position University of Pittsburgh Cancer Institute (UPCI) Director of the Centre for Cancer Immunology University of Southampton Research Technician II Weill Cornell College of Medicine More Science jobs from Drug Discovery EVENT 16th INTERNATIONAL CONFERENCE ON ALZHEIMER'S DRUG DISCOVERY 05.10.15 Jersey City, USA More science events from
PERSPECTIVES		Top
OPINION Prospects for the development of epigenetic drugs for CNS conditions Moshe Szyf p461 | doi:10.1038/nrd4580 Epigenetic mechanisms of gene regulation have an important role in brain development, and evidence is accumulating that some neurological, psychiatric and behavioural disorders can be triggered or maintained by epigenetic means. In this Perspective article, Moshe Szyf explores the epigenetic basis of disorders of the central nervous system (CNS) and discusses strategies for the development of epigenetic-targeted drugs for CNS indications, as well as the particular challenges associated with this approach. Abstract | Full Text | PDF
ANALYSIS		Top
An analysis of the attrition of drug candidates from four major pharmaceutical companies Michael J. Waring, John Arrowsmith, Andrew R. Leach, Paul D. Leeson, Sam Mandrell, Robert M. Owen, Garry Pairaudeau, William D. Pennie, Stephen D. Pickett, Jibo Wang, Owen Wallace & Alex Weir p475 | doi:10.1038/nrd4609 Attempts to reduce the number of efficacy- and safety-related failures that may be linked to the physicochemical properties of small-molecule drug candidates have been inconclusive owing to the limited size of data sets from individual companies. Waring and colleagues analyse the largest data set compiled so far on the causes of attrition for oral, small-molecule drug candidates, derived from a pioneering data-sharing effort by AstraZeneca, Eli Lilly and Company, GlaxoSmithKline and Pfizer. Abstract | Full Text | PDF | Supplementary information
REVIEWS		Top
Article series: Cancer immunotherapy Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: the force awakens Richard W. Childs & Mattias Carlsten p487 | doi:10.1038/nrd4506 Although natural killer (NK) cells can induce immune responses against malignancies, their therapeutic potential in the clinic is largely unexplored. In this Review, Childs and Carlsten discuss recent insights into NK cell biology and how these can be used for the development of new immunotherapeutic strategies against cancer. Abstract | Full Text | PDF
Article series: Cancer immunotherapy The pharmacology of second-generation chimeric antigen receptors Sjoukje J. C. van der Stegen, Mohamad Hamieh & Michel Sadelain p499 | doi:10.1038/nrd4597 Chimeric antigen receptors (CARs) provide a powerful means to augment T cell-based anticancer efficacy, and second-generation CARs have shown remarkable results in clinical trials. Here, the authors discuss the immunopharmacology of the different CAR constructs that are currently in clinical testing. Abstract | Full Text | PDF
CORRESPONDENCE		Top
Correspondence: Academic drug discovery within the United Kingdom: a reassessment Emma Shanks, Robin Ketteler & Daniel Ebner p510 | doi:10.1038/nrd4661 Full Text | PDF
Erratum: Oncolytic viruses get a boost with first FDA-approval recommendation Elie Dolgin p510 | doi:10.1038/nrd4680 Full Text | PDF
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*2013 Journal Citation Report (Thomson Reuters, 2014)

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