Drug Discovery@nature.com 31 August 2012

TABLE OF CONTENTS 31 August 2012 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter News Top Sting of Alzheimer's failures offset by upcoming prevention trials doi:10.1038/nrd3842 Three prevention trials in asymptomatic Alzheimer's disease patients will attempt to validate the amyloid hypothesis, evaluate biomarkers and set the stage for drug approvals. Full Text Europe sets out to reform its clinical trial rules doi:10.1038/nrd3843 A proposal to replace widely criticized trial regulations could boost European drug development, if key details can be sorted out. Full Text Regulatory watch: Pioneering gene therapy on brink of approval doi:10.1038/nrd3835 The Committee for Medicinal Products for Human Use of the EMA has now backed the approval of a gene therapy alipogene tiparvovec (Glybera, UniQure), for the treatment of LPL deficiency in patients with severe or multiple pancreatitis attacks. Full Text Trial watch: HIV integrase inhibitor-based regimen beats market leader doi:10.1038/nrd3836 Shionogi-ViiV Healthcare's dolutegravir-based regimen has demonstrated superiority over the most widely prescribed HIV combination therapy, Atripla (Gilead/BMS). Full Text Analysis Top Differentiating AMKL doi:10.1038/scibx.2012.857 Researchers have found that inhibiting Aurora-A induces cancer cell differentiation in acute megakaryoblastic leukemia, thus providing a therapeutic benefit in a mouse model of the disease. They hope to start clinical trials next summer. Full Text The pharmaceutical market for obesity therapies doi:10.1038/nrd3730 In the wake of the recent approvals of the first new obesity therapies in more than a decade, Wong and colleagues analyse their market prospects as well as the late-stage pipeline. Full Text Research Highlights Top Cancer: Passenger deletions create cancer-specific Achilles heel doi:10.1038/nrd3826 Cancer cells tend to shed tumour suppressor genes — and often delete neighbouring genes in the process. New research shows that genes deleted in cells that neighbour cancer cells create cancer cell-specific vulnerabilities that can be targeted by new anticancer strategies. Full Text Structure-based drug design: Opening the door to an epigenetic target doi:10.1038/nrd3827 A structure-guided approach has been used to identify the first specific small-molecule inhibitor of a jumonji histone demethylase. Full Text Ischaemic disorders: Nanotherapeutic delivers clot-busting drug doi:10.1038/nrd3828 Shear-activated nanotherapeutics can deliver thrombolytic drugs to the site of vascular occlusion, enabling rapid clot dissolution and an increase in survival in mouse models. Full Text Research & Reviews Top Autophagy modulation as a potential therapeutic target for diverse diseases doi:10.1038/nrd3802 This article provides an overview of the mechanisms and regulation of autophagy, the role of this pathway in disease and strategies for therapeutic modulation. Full Text Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons doi:10.1038/nrd3739 Emerging knowledge on the role of the hypothalamus may facilitate the discovery of new agents that are more effective than current anti-obesity drugs, and have an acceptable benefit–risk profile. Full Text Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis doi:10.1038/nchembio.1060 A small-molecule activator specific for PKM2 binds to a site distinct from the endogenous activator fructose-1,6-bisphosphate, promoting tetramerization and constitutive activation of PKM2, to inhibit xenograft tumor growth in mice. Full Text EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans doi:10.1038/nm.2901 Genetic or pharmacological inhibition of Epha4 is protective in rodent and zebrafish models of amyotrophic lateral sclerosis. In two patients, mutations in Epha4 are associated with longer survival, suggesting Epha4 may be targeted therapeutically. Full Text Drug Discovery JOBS of the week Ph.D. Scholarship in Brain Repair and Rehabilitation University of Newcastle Drug Discovery Researcher Monash University 4 Tenure Track Positions-Diagnostics, Targeted Therapy, Imaging Guided Therapy, Drug Delivery Georgia State University Postdoctoral Research Associate - Drug Metabolism and Pharmacokinetics Scripps Fl Principal Investigator positions in Biological Chemistry & Drug Discovery University of Dundee, College of Life Sciences More Science jobs from Drug Discovery EVENT Autophagy as a Therapeutic Target in Multiple Diseases: From Molecular Mechanisms to Drug Discovery 25.09.12 NY, US 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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