Nature Reviews Drug Discovery contents May 2012 Volume 12 Number 5 pp 333-419

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TABLE OF CONTENTS
May 2012 Volume 11 Number 5
Impact Factor 28.712 *	In this issue Comment News and Analysis Research Highlights Perspectives Reviews Correspondence Also this month Article series: A guide to drug discovery Case Histories  Featured article: Epigenetic protein families: a new frontier for drug discovery Cheryl H. Arrowsmith, Chas Bountra, Paul V. Fish, Kevin Lee & Matthieu Schapira
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Nature Reviews Cancer POSTER - MITOCHONDRIAL FUNCTION AND CANCER Author: Douglas C. Wallace This Poster highlights some recent discoveries that have led to a renewed interest in the function of mitochondria in cancer cells. Mitochondria carry out a number of crucial functions in cells and these can be altered through mutations in either the nuclear DNA or the mitochondrial DNA. Access the Poster FREE online! www.nature.com/nrc/posters/mitochondria This Poster is freely available thanks to sponsorship from Abcam
In this issue p333 | doi:10.1038/nrd3724 Full Text
Comment: Innovation and value-driven engineering Frank L. Douglas p335 | doi:10.1038/nrd3725 Emerging strategies to simultaneously catalyse rewardable innovation in the field of medical devices and reduce health-care costs could also be applicable in drug development. Abstract | Full Text | PDF
NEWS AND ANALYSIS		Top
Anti-NGF painkillers back on track? David Holmes p337 | doi:10.1038/nrd3732 Following an FDA advisory committee vote to restart clinical development of nerve growth factor antagonists, could this novel class of analgesics still fulfil its once-anticipated potential? PDF
Oncology trials gear up for high-throughput sequencing Asher Mullard p339 | doi:10.1038/nrd3733 Researchers are starting to use high-throughput genomic technologies to guide patients into trials of experimental cancer therapies, but is our understanding of the cancer genome ready yet? PDF
NEWS IN BRIEF PCSK9 inhibitor space starts to heat up | Interleukin-17 double take | More CV data needed for obesity drugs, says panel p341 | doi:10.1038/nrd3734 PDF
BIOBUSINESS BRIEFS Deal watch: Alcon invests in first non-surgical therapy for common eye disorder Sarah Crunkhorn p342 | doi:10.1038/nrd3736 PDF
BIOBUSINESS BRIEFS Trial watch: Genetic association studies link interleukin-6 receptor to coronary heart disease Charlotte Harrison p342 | doi:10.1038/nrd3737 PDF
PATENT WATCH Drug dosage patent ban casts doubt on diagnostics | Mixed results for Seroquel XR patents | Bromodomain-containing proteins Charlotte Harrison p344 | doi:10.1038/nrd3735 PDF
AN AUDIENCE WITH Stephen Frye p346 | doi:10.1038/nrd3726 Stephen Frye, from the University of North Carolina in Chapel Hill, USA, discusses emerging capabilities of academic drug discoverers. PDF
FROM THE ANALYST'S COUCH Drug development risk and the cost of capital Aris I. Baras, Alex S. Baras & Kevin A. Schulman p347 | doi:10.1038/nrd3722 This article analyses the relationship between risk and the cost of capital for projects in different stages of drug development and describes a framework that could improve portfolio optimization strategies. PDF
FRESH FROM THE PIPELINE Ivacaftor Pamela B. Davis, Uma Yasothan & Peter Kirkpatrick p349 | doi:10.1038/nrd3723 First disease-modifying drug approved in the United States for the treatment of cystic fibrosis in patients with a specific mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator. PDF
RESEARCH HIGHLIGHTS Top Neurodegenerative disease: Taming the RAGE of Alzheimer's disease p351 | doi:10.1038/nrd3727 PDF Anticancer drugs: Epigenetic reprogramming sensitizes leukaemia to drug treatment p352 | doi:10.1038/nrd3729 PDF Neurodegenerative disease: The stress of misfolding p352 | doi:10.1038/nrd3731 PDF Cancer genomics: Constructing a 'cancerpaedia' p353 | doi:10.1038/nrd3730 PDF Neuromuscular disorders: Turning up the heat (shock) p354 | doi:10.1038/nrd3728 PDF IN BRIEF Lead discovery: Small-molecule inhibitors of cytoplasmic dynein | Cancer: Intratumour heterogeneity | Antibacterial drugs: Overcoming MRSA resistance | Anticancer drugs: Identifying tumour-assocated antigens PDF Drug Discovery JOBS of the week PhD Positions available in nanomaterials, intelligent nanomembranes, foldable devices and drug delivery Monash University , Alfred Hospital Research Associate - Discovery Immunology Genentech Human recombinant tyrosinase: a testing bench for new drugs to treat melanin-related disorders. Università di Padova- Team Leader Assay Technology - Therapeutic Antibody Discovery Kymab Post-Doctoral (WW) - Target Identification and Drug Discovery - Immunobiology and Cancer Research Program (W Wang) Oklahoma Medical Research Foundation (OMRF) More Science jobs from Drug Discovery EVENT Practical Aspects of Small Molecule Drug Discovery: At the interface of biology, chemistry and pharmacology 17.-22.06.12 Cambridge, UK More science events from
PERSPECTIVES		Top
Article series: A guide to drug discovery Finding the sweet spot: the role of nature and nurture in medicinal chemistry Michael M. Hann & György M. Keserü p355 | doi:10.1038/nrd3701 Extensive analyses of successful and failed compounds in drug discovery and development have improved our understanding of the role of physicochemical properties in attrition. They have also clarified the difficulties in finding the 'sweet spot' in medicinal chemistry programmes. Hann and Keserü discuss scientific, strategic and cultural considerations for medicinal chemistry practices, with the aim of promoting more effective use of what is already known, and a wider appreciation of the risks of pursuing suboptimal compounds. Abstract | Full Text | PDF | Supplementary information
REVIEWS		Top
The biology and therapeutic targeting of the proprotein convertases Nabil G. Seidah & Annik Prat p367 | doi:10.1038/nrd3699 The human proprotein convertases are a family of nine serine proteases that are involved in the processing and modulation of various proteins. Seidah and Prat review the physiological functions and pathological implications of proprotein convertases, highlighting recent advances and associated challenges in the development of novel therapeutics targeting them, including inhibitors of proprotein convertase subtilisin kexin 9 (PCSK9) for the treatment of hypercholesterolaemia. Abstract | Full Text | PDF
Epigenetic protein families: a new frontier for drug discovery Cheryl H. Arrowsmith, Chas Bountra, Paul V. Fish, Kevin Lee & Matthieu Schapira p384 | doi:10.1038/nrd3674 Epigenetic regulation of gene expression can contribute to diseases such as cancer, inflammation and neuropsychiatric disorders. Here, the authors review the protein families that mediate epigenetic signalling through histone acetylation and methylation, and highlight progress in the pharmacological modulation of each class of proteins. Abstract | Full Text | PDF | Supplementary information
Article series: Case Histories Bench to bedside: elucidation of the OPG–RANK–RANKL pathway and the development of denosumab David L. Lacey, William J. Boyle, W. Scott Simonet, Paul J. Kostenuik, William C. Dougall, John K. Sullivan, Javier San Martin & Roger Dansey p401 | doi:10.1038/nrd3705 In this Case History, Lacey and colleagues chronicle the events that led to an increased understanding of osteoclast biology, beginning with the identification of the pathway mediated by osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL) and RANK. They discuss the strategies that were followed to target this pathway, culminating in the development of the RANKL-specific antibody denosumab, which is now approved for the treatment of osteoporosis and the prevention of cancer-related skeletal events. Abstract | Full Text | PDF
CORRESPONDENCE		Top
Correspondence: Measuring the value of public–private partnerships in the pharmaceutical sciences Tom. R. Denee, Arnold Sneekes, Pieter Stolk, Antoine Juliens, Jan A. M. Raaijmakers, Michel Goldman, Daan J. A. Crommelin & Jorg W. Janssen p419 | doi:10.1038/nrd3078-c1 Full Text | PDF | Supplementary information
Correspondence: Experience and further development with the Voluntary Harmonization Procedure for multinational clinical trials in the European Union Hartmut Krafft, Chantal Bélorgey & Gudrun Szalay p419 | doi:10.1038/nrd3202-c2 Full Text | PDF
Correspondence: Glybera and the future of gene therapy in the European Union Norman Miller p419 | doi:10.1038/nrd3572-c1 Full Text | PDF
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