Drug Discovery@nature.com 19 October 2012

TABLE OF CONTENTS 19 October 2012 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement Weekly content now available Open Access - Peer Review - Renowned International Editorial Board Newly launched, CPT: PSP publishes weekly content covering the latest advances in quantitative methods as applied in pharmacology, physiology, and therapeutics in humans with a common focus on the application of these two areas on drug development.   News Top An audience with: Michael Snyder doi:10.1038/nrd3867 The Director of the Stanford Center for Genomics and Personalized Medicine discusses how the ENCODE project to build a comprehensive list of functional elements in the human genome could impact drug discovery. Full Text The new drug circuit doi:10.1038/nm1012-1452 Synthetic biology has historically relied on bacteria as a testing ground. Now, researchers are aiming to reprogram mammalian cells for a new generation of tailor-made treatments. Full Text Big players jostle for pole position in muscular dystrophy doi:10.1038/nbt1012-904b Recent deals and positive clinical data are sparking interest from investors and companies. Full Text Clinical setbacks reduce IGF-1 inhibitors to cocktail mixers doi:10.1038/nbt1012-906c Although monoclonal antibodies targeting IGF-1 have produced disappointing results, there is still potential for other approaches. Full Text Analysis Top Ember: warming up to brown fat doi:10.1038/scibx.2012.1045 Inhibiting a cation channel caused white fat cells to behave like brown fat, protecting mice from diet-induced obesity. Ember Therapeutics has options to in-license the findings as a part of a trio of new deals for brown fat–related targets. Full Text From the analyst's couch: Autism spectrum disorders doi:10.1038/nrd3771 This analysis looks at the increasing number of candidates in the pipeline for autism spectrum disorders, reflecting the increasing prevalence of autism and the growing interest in finding novel treatments. Full Text Research Highlights Top Neurodegenerative diseases: Anti-epileptic drug shows benefit in AD mouse model doi:10.1038/nrd3850 Using a mouse model engineered to overexpress human amyloid precursor protein and amyloid-β, researchers have shown that cognitive and synaptic deficits are caused by aberrant neuronal network activity, and that this can be improved with an anti-epileptic drug. Full Text Vaccines: Self-amplifying RNA in lipid nanoparticles: a next-generation vaccine? doi:10.1038/nrd3854 A new vaccine platform based on self-amplifying RNA encapsulated in synthetic lipid nanoparticles overcomes some of the limitations of earlier nucleic-acid-based approaches. Full Text Metabolic disorders: Safe cannabinoid receptor modulators in sight? doi:10.1038/nrd3851 A peripherally selective CB1R inverse agonist can safely and effectively reduce body weight in a mouse model of obesity, without affecting behaviour. Full Text Research & Reviews Top Targeting the TGFβ signalling pathway in disease doi:10.1038/nrd3810 This Review considers why the TGFβ signalling pathway is a drug target, the potential clinical applications of TGFβ inhibition, the issues arising with anti-TGFβ therapy and how these might be tackled. Full Text Targeting cells in chronic inflammation doi:10.1038/nrd3794 This Review focuses on the current knowledge of the IL-17–TH17 cell pathway to better understand the positive as well as potential negative consequences of targeting them. Full Text Naratriptan mitigates CGRP1-associated motor neuron degeneration caused by an expanded polyglutamine repeat tract doi:10.1038/nm.2932 Researchers describe a molecular cascade whereby mutant androgen receptor upregulates CGRP in neuronal cells, promoting JNK activation and degeneration. The 5-HT1B/1D receptor agonist naratriptan decreases CGRP expression and improves motor performance in a mouse model of SBMA. Full Text Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function doi:10.1038/nchembio.1081 Researchers propose that compounds binding a newly discovered allosteric site of the hepatitis C virus’s NS3 protein may inhibit its function, and thus represent a new class of direct-acting antiviral agents. Full Text Drug Discovery JOBS of the week Post Doctoral Fellowship � Bacterial Pathogenesis and Antimicrobial Drug Discovery Beth Israel Deacon Medical Center - Harvard Medical School Postdoctoral Fellowship in Synthetic Cell-Based Screening / Microfluidics / Drug Discovery The Scripps Research Institute (TSRI) Post Doctoral Fellowship � Bacterial Pathogenesis and Antimicrobial Drug Discovery Beth Israel Deacon Medical Center - Harvard Medical School Drug Discovery Opportunities D. E. Shaw Research, LLC Scientist / Sr Scientist � Oncology Drug Discovery H3 Biomedicine More Science jobs from Drug Discovery EVENT 11th Annual World Drug Manufacturing Summit 2012 26.-28.11.12 Dusseldorf, Germany 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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