Nature Reviews Drug Discovery contents September 2013 Volume 12 Number 9 pp 645 - 719

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TABLE OF CONTENTS
September 2013 Volume 12 Number 9
Impact Factor 33.078 *	In this issue Comment News and Analysis Research Highlights Reviews Correspondence Also this month Posters: Strategies to increase pancreatic β-cell mass and function Targeting inflammation in diabetes  Featured article: 50 years of hurdles and hope in anxiolytic drug discovery Guy Griebel & Andrew Holmes
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In this issue p645 | doi:10.1038/nrd4113 Full Text
Comment: Appropriate evidence for adaptive marketing authorization Jean Philippe de Jong, Diederick E. Grobbee, Bruno Flamion, Susan R. Forda & Hubert G. M. Leufkens p647 | doi:10.1038/nrd4114 Adaptive marketing authorization approaches may, in some instances, replace traditional binary regulatory decisions on drug approval with progressive reduction of uncertainty about the benefit-risk profile of a drug through iterative evidence gathering and evaluation. How should the nature of such evidence be determined? Full Text | PDF | Supplementary information
NEWS AND ANALYSIS		Top
Irreversible kinase inhibitors gain traction Katharine Sanderson p649 | doi:10.1038/nrd4103 The approval of Boehringer Ingelheim's anticancer drug afatinib highlights the growing enthusiasm for once-shunned irreversible kinase inhibitors. PDF
Patient-focused drug development programme takes first steps Asher Mullard p651 | doi:10.1038/nrd4104 First meetings see regulators and patient advocates start working to incorporate the perspective of patients into benefit-risk assessments. PDF
NEWS IN BRIEF First-in-class approval rate stays steady p653 | doi:10.1038/nrd4119 PDF
A comeback for anti-CD3s in type 1 diabetes? p653 | doi:10.1038/nrd4120 PDF
Improving animal research p653 | doi:10.1038/nrd4121 PDF
BIOBUSINESS BRIEFS Trial watch: Clinical trial boost for lentiviral gene therapy Monica Hoyos Flight p654 | doi:10.1038/nrd4111 PDF
BIOBUSINESS BRIEFS Regulatory watch: Speedy validation sought for new cardiotoxicity testing strategy Kelly Rae Chi p655 | doi:10.1038/nrd4112 PDF
PATENT WATCH Eli Lilly wins Alzheimer's antibody patent dispute p656 | doi:10.1038/nrd4122 PDF
Teva loses key MS drug patent Charlotte Harrison p656 | doi:10.1038/nrd4123 PDF
A longer patent life for formulated drugs in Australia? Charlotte Harrison p656 | doi:10.1038/nrd4124 PDF
Recent patents related to S1P Charlotte Harrison p657 | doi:10.1038/nrd4125 PDF
AN AUDIENCE WITH Tachi Yamada p658 | doi:10.1038/nrd4110 Tachi Yamada, Takeda's Chief Medical & Scientific Officer, discusses changes at Takeda and in the Japanese pharmaceutical industry. PDF
FROM THE ANALYST'S COUCH The epigenetics pipeline Vivian A. DeWoskin & Ryan P. Million p661 | doi:10.1038/nrd4091 Epigenetic alterations are found in a number of diseases. This analysis explores the different approaches that are being pursued to exploit the therapeutic potential of epigenetic targets, and provides an overview of the current epigenetics pipeline. PDF
RESEARCH HIGHLIGHTS Top Cancer: Special delivery service p663 | doi:10.1038/nrd4107 PDF Neurodegenerative disorders: Linking apolipoprotein E to LOAD p664 | doi:10.1038/nrd4106 PDF Kinase inhibitors: A molecular target for myelodysplastic syndromes p664 | doi:10.1038/nrd4108 PDF G protein-coupled receptors: A double attack on pain p665 | doi:10.1038/nrd4105 PDF HIV: Efficacy through BibNAbs p666 | doi:10.1038/nrd4109 PDF IN BRIEF Analgesia: Targeting the EP3 receptor to combat pain | Gene therapy: Decoy viral capsids boost vector delivery | Heart disease: Tacrolimus shows promise in PAH models | Drug properties: A method to measure target engagement in cells PDF Drug Discovery JOBS of the week Laboratory Head / Senior Scientist Insulin Biology (m / f) Sanofi-Aventis Deutschland GmbH Tenure Track Researcher Tokai University Postdoctoral Positions Boston University Research Associate II Johnson & Johnson More Science jobs from Drug Discovery EVENT Malaria Drug Development and Resistance Control 03.07.14 London, UK More science events from
REVIEWS		Top
50 years of hurdles and hope in anxiolytic drug discovery Guy Griebel & Andrew Holmes p667 | doi:10.1038/nrd4075 Vast efforts have been made to develop novel anxiolytic drugs that improve on those that target the GABA ([gamma]-aminobutyric acid)-benzodiazepine system, but promising results in rodents have rarely translated into effectiveness in humans. Griebel and Holmes analyse the major trends from a database of published preclinical studies on novel anxiolytic agents in the past 50 years, highlight issues that may have hampered progress and offer recommendations to improve anxiolytic drug discovery. Abstract | Full Text | PDF | Supplementary information
Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond Gregory T. Kunkel, Michael Maceyka, Sheldon Milstien & Sarah Spiegel p688 | doi:10.1038/nrd4099 Sphingosine-1-phosphate (S1P) has a key role in the control of immune cell trafficking and is involved in disorders including cancer and inflammatory diseases. Here, Spiegel and colleagues discuss the ways in which S1P could be therapeutically targeted and highlight recent data from preclinical studies and clinical trials. Abstract | Full Text | PDF
Targeting the unfolded protein response in disease Claudio Hetz, Eric Chevet & Heather P. Harding p703 | doi:10.1038/nrd3976 Stress induced by the accumulation of unfolded proteins in the endoplasmic reticulum (ER) is observed in many diseases, including cancer, diabetes and neurodegenerative disorders. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR). Hetz and colleagues discuss the opportunities to modulate components of UPR signalling to therapeutically manipulate levels of ER stress in disease. Abstract | Full Text | PDF
CORRESPONDENCE		Top
Correspondence: Regulatory evaluation of Glybera in Europe — two committees, one mission Daniela Melchiorri, Luca Pani, Paolo Gasparini, Giulio Cossu, Janis Ancans, John Joseph Borg, Catherine Drai, Piotr Fiedor, Egbert Flory, Ian Hudson, Hubert G. Leufkens, Jan Müller-Berghaus, Gopalan Narayanan, Brigitte Neugebauer, Juris Pokrotnieks, Jean-Louis Robert, Tomas Salmonson & Christian K. Schneider p719 | doi:10.1038/nrd3835-c1 Full Text | PDF
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*2012 Journal Citation Report (Thomson Reuters, 2013)

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