Drug Discovery@nature.com 11 January 2013

TABLE OF CONTENTS 11 January 2013 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement The January 2013 of APS (Acta Pharmacologica Sinica) contains a special section on stroke, which covers our current understanding of the pathophysiological roles of the ion channels and exchangers involved in non-glutamate mechanisms in cerebral ischemia and stroke, as well as their potential for therapeutic intervention. Access the Special Issue on Stroke today!   News Top Fragment-based lead discovery grows up doi:10.1038/nrd3926 With multiple drug candidates in the clinic that originated from fragment-based lead discovery, the approach of starting small has become big. Full Text 2012 in reflection doi:10.1038/nrd3927 Last year saw the largest loss of revenue yet from major drugs due to patent expiries, but a continuation of 2011's higher level of drug approvals and new initiatives to address R&D challenges provide hope for the future. Full Text Market watch: Upcoming market catalysts in Q1 2013 doi:10.1038/nrd3928 These include an approval decision on ponatinib, as well as top-line Phase III data for ThermoDox, and a potential disease-modifying therapy for Alzheimer's disease. Full Text Trial watch: Enzyme replacement success in Phase III trial for rare metabolic disorder doi:10.1038/nrd3929 BioMarin Pharmaceuticals has recently announced positive results from the Phase III trial of its enzyme replacement therapy BMN-100 for the treatment of mucopolysaccharidosis type IVA (Morquio A syndrome). Full Text Analysis Top Translating mRNA vaccines doi:10.1038/scibx.2012.1273 CureVac and the Friedrich Loeffler Institute have in vivo evidence that an mRNA-based vaccine can prevent influenza A infection. The results provide proof of concept for the company's vaccine platform in infectious disease, and Sanofi has options to the technology. Full Text Alzheimer's disease market: hope deferred doi:10.1038/nrd3922 The last few months have seen a flurry of trial results for investigational agents in Alzheimer's disease. This analysis investigates the different categories of developmental drugs, and provides an outlook to the future of the market. Full Text Research Highlights Top Lung disorders: A new model and modulator of pulmonary oedema doi:10.1038/nrd3917 Two complementary studies have identified a new microdevice model — termed 'lung on a chip' — of pulmonary oedema, and identified a blocker of TRPV4 that inhibits pulmonary oedema in animal models. Full Text Immunotherapy: Immunological bullets against Alzheimer's disease doi:10.1038/nrd3919 The exact contribution of innate immune signalling to Alzheimer’s disease pathogenesis is still unclear. Now, researchers have identified IL-12 and IL-23 signalling as a therapeutic target in this neurodegenerative disorder. Full Text Neurological disorders: Targeting translation in autism doi:10.1038/nrd3915 A study in Nature shows that pharmacological inhibition of eIF4E activity or siRNA-mediated knockdown of neuroligin 1 are novel potential targets for the treatment of Autism Spectrum Disorders. Full Text Research & Reviews Top Objective assessment of cancer genes for drug discovery doi:10.1038/nrd3913 This article describes and demonstrates an objective, systematic computational assessment of biological and chemical space. The approach can be applied to any human gene set to prioritize targets for further evaluation. Full Text Kynurenines in the CNS: recent advances and new questions doi:10.1038/nrd3793 This Review describes the role of the kynurenine pathway in the pathology of Huntington's disease, migraine and multiple sclerosis, and highlights the most promising compounds that could be of therapeutic value. Full Text Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance doi:10.1038/nm.3056 As expression of TRIP-Br2 is elevated in fat from obese humans, TRIP-Br2 might be a new therapeutic target against insulin resistance and hyperlipidemia. Full Text ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets doi:10.1038/nm.3048 The authors have engineered anti-BCL drugs to reduce platelet toxicity. Their compound is effective in several tumor models in vivo and had reduced toxicity in three patients with refractory leukemia. Full Text Drug Discovery JOBS of the week Postdoctoral Fellow - Drug Discovery Moffitt Cancer Center Postdoctoral Fellow in Drug Delivery Vanderbilt University Faculty of Science - Lecturer in Drug Delivery - 2 Posts University of East Anglia Research Chair in Rational Drug Design College of Pharmacy and Nutrition, University of Saskatchewan Post-Doctoral Research Fellow Fred Hutchinson Cancer Research Center (FHCRC) More Science jobs from Drug Discovery EVENT Translating Natural Products into Drugs for Alzheimer’s and Neurodegenerative Disease 06.05.12 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. Full Text Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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