Nature Reviews Drug Discovery contents December 2014 Volume 13 Number 12 pp 871-942

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TABLE OF CONTENTS
December 2014 Volume 13 Number 12		Advertisement
Impact Factor 37.231 *	In this issue Comment News and Analysis Research Highlights Reviews Correspondence Also this month  Featured article: SCF ubiquitin ligase-targeted therapies Jeffrey R. Skaar, Julia K. Pagan & Michele Pagano	Where is Your Protein on the Ubiquitin-Proteasome Pathway? Identify, inhibit, and measure ubiquitination with Cayman's antibodies, inhibitors, and assay kits. Focus on deubiquitinases to explore dynamic ubiquitination in regulating protein stability, ubiquitin homeostasis, and cell signaling.
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Comment: Securing the future of drug discovery for central nervous system disorders Peter Høngaard Andersen, Richard Moscicki, Barbara Sahakian, Rémi Quirion, Ranga Krishnan, Tim Race & Anthony Phillips, on behalf of the 2013 CINP Summit Group p871 | doi:10.1038/nrd4489 Innovative partnerships among researchers, patients, regulators, payors and industry are needed to reinvigorate drug discovery for central nervous system disorders. Here, we summarize plans of the Collegium Internationale Neuro-Psychopharmacologicum (CINP) to achieve this goal. Full Text | PDF | Supplementary information
NEWS AND ANALYSIS		Top
Breakthrough programme turns two Asher Mullard p873 | doi:10.1038/nrd4487 The breakthrough designation cohort shows no signs of slowed growth, as the FDA grants 'all-hands-on-deck' attention to a total of 68 therapeutics. PDF
Drug discoverers chart path to tackling data irreproducibility Elie Dolgin p875 | doi:10.1038/nrd4488 Researchers from across the biomedical research community met in October to discuss solutions to the 'irreproducibility epidemic', which has been re-emphasized by new data from Novartis and Sigma-Aldrich. PDF
NEWS IN BRIEF New drugs cost US$2.6 billion to develop Asher Mullard p877 | doi:10.1038/nrd4507 PDF
European regulators approve first PARP inhibitor Asher Mullard p877 | doi:10.1038/nrd4508 PDF
Phase III setback for lead angiopoietin inhibitor Asher Mullard p877 | doi:10.1038/nrd4509 PDF
BIOBUSINESS BRIEFS Regulatory watch: Outcomes of EMA marketing authorization applications: does partnering have an influence? Cornelis A. van den Bogert, Patrick C. Souverein, Michelle Putzeist, Hubert G. M. Leufkens, Susan W. J. Janssen & Gerard H. Koëter p878 | doi:10.1038/nrd4468 PDF
Trial watch: Self-inactivating gene-therapy vector alleviates safety concerns Megan Cully p879 | doi:10.1038/nrd4495 PDF
Deal watch: Genentech dives deeper into the next wave of cancer immunotherapies Sarah Crunkhorn p879 | doi:10.1038/nrd4502 PDF
AN AUDIENCE WITH Doug Williams p880 | doi:10.1038/nrd4496 Doug Williams, head of Research and Development at Biogen Idec, discusses remyelinating agents, Alzheimer's disease drugs and gene therapy. PDF
FROM THE ANALYST'S COUCH The immune checkpoint inhibitors: where are we now? Rachel M. Webster p883 | doi:10.1038/nrd4476 Checkpoint inhibitors, which stimulate the anticancer activity of T cells, are the most advanced class of cancer immunotherapies. This analysis examines the pipeline of agents in development and their market potential. PDF
RESEARCH HIGHLIGHTS Top Metabolic disease: Mitochondrial uncoupler reverses diabetes p885 | doi:10.1038/nrd4491 PDF Obesity: Adenosine protects from diet-induced obesity p886 | doi:10.1038/nrd4490 PDF Sepsis: PCSK9 blockade helps clear pathogenic lipids p886 | doi:10.1038/nrd4492 PDF Neurodegenerative disease: New dimensions in Alzheimer's modelling p887 | doi:10.1038/nrd4494 PDF Cancer: New delivery platform targets antimirs to tumours p888 | doi:10.1038/nrd4493 PDF IN BRIEF Metabolic disease: Weight loss herb targets GPCR | Type 2 diabetes: Personalizing therapy | Natural products: Global classification of NPGCs | Type 2 diabetes: New lipid class regulates glucose homeostasis PDF Drug Discovery JOBS of the week Postdoctoral Fellow Moffitt Cancer Center & Research Institute Postdoctoral Fellowships in Cancer Computational Biology: Targeting Tumor Epi-Stroma Interactions Princess Margaret Cancer Centre Postdoctoral Position in Microbiology Virginia Commonwealth University Postdoctoral Research Associate University of Illinois Chicago College of Medicine Postdoctoral Scholar position University of California - San Francisco More Science jobs from Drug Discovery EVENT Advances & Progress in Drug Design 16.02.15 London, UK More science events from
REVIEWS		Top
SCF ubiquitin ligase-targeted therapies Jeffrey R. Skaar, Julia K. Pagan & Michele Pagano p889 | doi:10.1038/nrd4432 Inhibition of E3 ubiquitin ligases, which provide substrate specificity to the ubiquitin proteasome system, is an attractive strategy to inhibit the degradation of a small subset of proteins. Skaar et al. discuss the progress that has been made in the development of therapeutic inhibitors of E3 ligases, in particular the SKP1-CUL1-F box protein (SCF) ubiquitin ligase complexes, and the challenges that lie ahead. Abstract | Full Text | PDF
Is there new hope for therapeutic matrix metalloproteinase inhibition? Roosmarijn E. Vandenbroucke & Claude Libert p904 | doi:10.1038/nrd4390 The failure of many clinical trials of the pioneering matrix metalloproteinase (MMP) inhibitors in oncology owing to lack of efficacy and side effects, such as musculoskeletal toxicity, reduced enthusiasm for further development of the drug class. Vandenbroucke and Libert discuss how greater knowledge of MMP biology, as well as the development of more specific MMP inhibitors, could provide new opportunities to use such agents in the treatment of sepsis and other inflammatory disorders. Abstract | Full Text | PDF | Supplementary information
Targeting RAS-ERK signalling in cancer: promises and challenges Ahmed A. Samatar & Poulikos I. Poulikakos p928 | doi:10.1038/nrd4281 Mutations in components of the ERK pathway are a common occurrence in human cancer. Several drugs that target components of the ERK signalling cascade such as RAF, MEK and ERK have been approved or are in late-stage clinical development, and advances are being made in developing RAS inhibitors. Here, Samatar and Poulikakos discuss the particular challenges associated with each target and provide an overview of agents in development. Abstract | Full Text | PDF
CORRESPONDENCE		Top
Correspondence: A novel approach for establishing cardiovascular drug efficacy Hiddo. J. Lambers Heerspink, Diederick E. Grobbee & Dick de Zeeuw p942 | doi:10.1038/nrd4090-c2 Full Text | PDF | Supplementary information
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*2013 Journal Citation Report (Thomson Reuters, 2014)

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