Drug Discovery@nature.com 15 June 2012

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TABLE OF CONTENTS 15 June 2012 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement Nature Reviews Cancer & Nature Reviews Immunology FOCUS ON TUMOUR IMMUNOLOGY & IMMUNOTHERAPY Access the Focus online for FREE until end of September 2012: www.nature.com/reviews/focus/tumourimmunology Produced with support from Boehringer Ingelheim www.boehringer-ingelheim.com   News Top Proof of concept for next-generation nanoparticle drugs in humans doi:10.1038/nbt0612-471 The results from several human studies may provide the first proof of concept that new nanoparticle-based modalities can optimize the pharmacological and therapeutic profiles of existing drugs. Full Text Agency defies advice and rejects gene therapy for third time doi:10.1038/nbt0612-474b The refusal, for the third time, by the European Medicines Agency to recommend approval of Glybera, a treatment for the inherited disorder lipoprotein lipase deficiency, means there's still no approved gene therapy in a regulated Western market. Full Text Anti-IL-17 mAbs herald new options in psoriasis doi:10.1038/nbt0612-475 Antibodies against interleukin-17 and its receptor have shown outstanding efficacy in phase 2 psoriasis trials. Full Text Cancer drug's survivin suppression called into question doi:10.1038/nm0612-842b New data are emerging from preclinical tests to suggest that YM155, a putative antisurvivin agent from Japan's Astellas Pharma, might not be working exactly as first anticipated. Full Text Analysis Top Two-pronged approach to T1D doi:10.1038/scibx.2012.588 A team that has reversed advanced type 1 diabetes in mice by combining a method to regenerate pancreatic β cells with a strategy to induce immune tolerance plans to validate the technique in other autoimmune diseases before applying it to patients with type 1 diabetes. Full Text Pipeline pioneers: Vismodegib doi:10.1038/nrd3753 First-in-class inhibitor of the Hedgehog signalling pathway approved in the United States for the treatment of basal cell carcinoma. Full Text From the analyst's couch: Outlook for the next 5 years in drug innovation doi:10.1038/nrd3744 Analysis of industry pipeline data and revenue forecasts highlights several trends in the anticipated output of new drugs and the therapeutic area focus over the next 5 years, including a growth in the average number of new drug approvals annually. Full Text Research Highlights Top Neurological disorders: Nanoparticle opens door to cerebral palsy treatment doi:10.1038/nrd3758 Polyamidoamine dendrimers have been used to effectively deliver an anti-inflammatory drug to the brain of a rabbit model of cerebral palsy, resulting in improved motor function. Full Text Bone diseases: SEMA3A strikes a balance in bone homeostasis doi:10.1038/nrd3759 Researchers have identified semaphorin 3A as a dual regulator of osteoclasts and osteoblasts, and suggest that this could provide a strategy to address limitations of existing osteoporosis drugs that target osteoclast activity. Full Text Therapeutics: Iterations of BRAF doi:10.1038/nrc3284 Röring and colleagues investigate the involvement of the dimer interface in the ability of RAF to mediate downstream signalling, with implications for targeting BRAF. Full Text Research & Reviews Top Are sirtuins viable targets for improving healthspan and lifespan? doi:10.1038/nrd3738 This article provides an overview of the sirtuin family, focusing on sirtuin 1 and its potential to be targeted in the treatment of age-related diseases. Full Text Spatial regulation of receptor tyrosine kinases in development and cancer doi:10.1038/nrc3277 This Review discusses how dysregulation of the spatial control of receptor tyrosine kinase (RTK) activity might contribute to tumorigenesis and affect the sensitivity and resistance of cancers to pharmacological RTK inhibitors. Full Text Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing doi:10.1038/nbt.2214 Whitehead et al. demonstrate that computational design followed by comprehensive energy landscape mapping can generate proteins with potential therapeutic utility. Full Text Direct and selective small-molecule activation of proapoptotic BAX doi:10.1038/nchembio.995 A computational screen identifies a small-molecule activator of proapoptotic BAX that selectively binds to the BAX trigger site, inducing characteristic conformational changes, oligomerization and BAX-dependent cell death. Full Text Drug Discovery JOBS of the week PhD Opportunity within the ITN "TRAIN-ASAP" Veterinary drug development in the field of antimicrobial resistance, Paris - FRANCE DA VOLTERRA Metabolomics of fungal diseases: a systems biology approach for biomarkers discovery and therapy. Dipartimento di Medicina Sperimentale e Scienze Biochimiche Senior Scientist, Gene Discovery Hudosn Shribman Scientific Recruitment Postdoctoral Fellow in Drug Delivery Vanderbilt University Department of Biomedical Engineering 4 Tenure Track Positions-Diagnostics, Targeted Therapy, Imaging Guided Therapy, Drug Delivery Georgia State University More Science jobs from Drug Discovery EVENT New Drug Product Development and Lifecycle Management 06.-07.08.12 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 Advertisement SciBX: Science-Business eXchange is a weekly publication that identifies and analyzes the most important translational research articles from over 40 journals. Find out which papers have real scientific and commercial potential, and why. 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