Drug Discovery@nature.com 10 August 2012

TABLE OF CONTENTS 10 August 2012 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement Feel like your paper is lost in a sea of submissions? Scientific Reports publishes your research quickly and efficiently, and makes it freely available to the global scientific community. Learn more with our one minute illustrative video.   News Top Genentech's Alzheimer's antibody trial to study disease prevention doi:10.1038/nbt0812-731 The first clinical trial of a drug's ability to forestall Alzheimer's disease in cognitively healthy individuals is preparing to launch, testing Genentech's crenezumab. Full Text T-DM1 impresses at ASCO doi:10.1038/nbt0812-728 The data from Genentech's first phase 3 trial of T-DM1 is providing a boost for the burgeoning field of antibody-drug conjugates. Full Text Gilead/BMS ponder HCV combo doi:10.1038/nbt0812-735b Gilead Sciences is still deciding whether to combine its antiviral GS-7977 for hepatitis C virus with Bristol-Myers Squibb's daclatasvir in a phase 3 trial. Full Text Shire punts on bioscaffolds for cell-based regenerative medicine doi:10.1038/nbt0812-727 Shire's recent interest in biomaterials reflects a growing understanding of how to apply biomaterials to effectively deliver factors and cells for a variety of therapeutic applications. Full Text Analysis Top Cylene takes pol position in cancer doi:10.1038/scibx.2012.774 Researchers have shown that a small molecule inhibitor of RNA polymerase I blocked tumor growth in mouse models of lymphoma. Cylene Pharmaceuticals and the Peter MacCallum Cancer Centre plan to start a Phase I trial. Full Text Fresh from the pipeline: Pasireotide doi:10.1038/nrd3788 In April 2012, pasireotide was granted European marketing authorization for the treatment of Cushing's disease, providing a new option for patients for whom surgery has failed. Full Text From the analyst's couch: A new dawn in the sleep disorders pipeline? doi:10.1038/nrd3789 This analysis article looks at the growing interest in novel molecular targets for sleep disorders, and the market opportunities in this area of significant unmet need. Full Text Research Highlights Top Cancer: PD1 makes waves in anticancer immunotherapy doi:10.1038/nrd3806 Two papers describe early-stage clinical trials of two monoclonal antibodies that target signalling through the T cell co-inhibitory receptor programmed cell death protein 1, suggesting that such antibodies might provide a new benchmark for anticancer immunotherapy. Full Text Metabolic disorders: New target for appetite control doi:10.1038/nrd3803 The G protein-coupled receptor GPR17 has been identified as a direct target of the forkhead box protein O1 transcription factor, which activates AGRP-expressing neurons to regulate food intake in mice. Full Text Neurodegenerative disorders: Reversing Huntington's disease doi:10.1038/nrd3804 New research shows that transient infusion of single-stranded antisense oligonucleotides in a mouse model results in sustained improvements in motor function and behaviour. Full Text Research & Reviews Top Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases doi:10.1038/nrd3800 This review looks at current and future drugs that may be available to treat a broad range of inflammation-related conditions by blocking interleukin-1. Full Text G protein-coupled receptors for energy metabolites as new therapeutic targets doi:10.1038/nrd3777 This review summarizes the functions of several recently discovered metabolite-sensing GPCRs and discusses the emerging pharmacological agents being developed to target these for metabolic disorders. Full Text A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response doi:10.1038/nature11262 A paper in Nature provides encouragement for designing small-molecule inhibitors to allow selective pharmacological intervention across the JMJ family. Full Text MDM4 is a key therapeutic target in cutaneous melanoma doi:10.1038/nm.2863 A paper in Nature Medicine identifies MDM4 as a key determinant of impaired p53 function in human melanoma and designates MDM4 as a promising target for antimelanoma combination therapy. Full Text Drug Discovery JOBS of the week Principal Investigator positions in Biological Chemistry & Drug Discovery University of Dundee, College of Life Sciences Institute Research Scientist � Drug Metabolism MD Anderson Cancer Center Postdoctoral Research Associate - Drug Metabolism and Pharmacokinetics Scripps Fl Postdoctoral Fellow, Drug Delivery / Formulation The Centre for Drug Research & Development (CDRD) Development of Drugs and Drug Delivery Systems for Inherited Retinal Degeneration University of Tübingen More Science jobs from Drug Discovery EVENT World Drug Safety Congress Europe 2012 11.-14.09.12 London, UK More science events from Careers Top Career snapshots archive Career snapshots feature people associated with drug discovery and drug development, with the aim of providing expert insights and advice on a wide range of positions and career paths in this field. 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