Drug Discovery@nature.com 17 February 2012

TABLE OF CONTENTS 17 February 2012 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement Nature Reviews Genetics ANIMATION ON RNA INTERFERENCE Nature Reviews Genetics, in association with Arkitek Studios, has brought RNAi to life in this vivid, audio-visual journey into the cell. See RNAi in action by viewing the animation for FREE at: www.nature.com/nrg/multimedia/rnai Produced with support from Thermo Scientific   News Top Cancer-causing mutations yield their secrets doi:10.1038/nature.2012.10029 Changes to metabolism disrupt cells' ability to differentiate. Full Text Sequencing set to alter clinical landscape doi:10.1038/482288a Access to whole genomes shifts potential for diagnosis, but poses challenges for doctors and regulators. Full Text Big pharma upheavals cast shadow across biotech sector doi:10.1038/nbt0212-119 The issues that are driving pharma's shifting and restructuring are exerting a profound influence on the ecosystem for private and public biotech companies. Full Text Toll-like receptor blocker slows beta cell death in type 1 diabetes doi:10.1038/nbt0212-124c Synthetic peptide meets primary and secondary end points in a Phase III trial in type 1 diabetes. Full Text Analysis Top Bringing on the BRAF doi:10.1038/scibx.2012.140 Independent findings from European and U.S. teams suggest combining BRAF inhibitors with EGFR inhibitors could treat colorectal cancers resistant to monotherapy with either type of drug. Both groups are now planning clinical trials with such combinations. Full Text Fresh from the Pipeline: Ruxolitinib doi:10.1038/nrd3652 In November 2011, ruxolitinib (Jakafi; Incyte/Novartis), a small-molecule inhibitor of Janus kinases, was approved by the US Food and Drug Administration for the treatment of patients with myelofibrosis. Full Text From the analyst's couch: The neuropathic pain market doi:10.1038/nrd3624 This article discusses the drug pipeline for neuropathic pain, for which the market is forecast to grow by 50% by 2020. Full Text Research Highlights Top Drug delivery: Encapsulation improves therapeutic stem cell action doi:10.1038/nrd3661 Therapeutic stem cells encapsulated in a biodegradable synthetic extracellular matrix show promise in mouse models of human glioblastoma surgical resection. Full Text Anticancer drugs: Keeping one step ahead doi:10.1038/nrd3664 A recent study proposes a new drug combination strategy to target drug-resistant chronic myeloid leukaemia. Full Text Psychiatric disorders: Why two is better than one doi:10.1038/nrn3181 The antidepressant fluoxetine increases synaptic plasticity in the amygdala and thereby facilitates fear erasure through extinction. Full Text Research & Reviews Top Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy doi:10.1038/nrd3628 This article outlines the challenges and opportunities for improving cognition in individuals suffering from psychiatric disorders, whose quality of life can be severely compromised by cognitive deficits. Full Text Targeting MET in cancer: rationale and progress doi:10.1038/nrc3205 Progress in understanding the structure and function of hepatocyte growth factor/scatter factor, MET and associated signalling components has led to the development of blocking antibodies and small-molecule MET kinase inhibitors, as discussed in this Review. Full Text Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates doi:10.1038/nbt.2108 Conjugating drugs to therapeutic antibodies is a promising strategy to increase their therapeutic efficacy. Shen et al. show that the local chemical environment of the conjugation site influences the in vivo stability and efficacy of the modified antibodies. Full Text Gap junction inhibition prevents drug-induced liver toxicity and fulminant hepatic failure doi:10.1038/nbt.2089 Liver toxicity is one of the most common reasons for abandoning new drugs in development or withdrawing approved drugs from the market. Patel et al. show that drug-induced liver injury can be limited in mice by a small-molecule inhibitor of the gap-junctional protein connexin 32. Full Text Drug Discovery JOBS of the week Postdoctoral Fellow Deeley Research Centre, BC Cancer Agency Postdoctoral scholarship for studies on cancer cell-derived exosomes Karolinska Institutet, Stockholm, Sweden PhD positions in Moleculare Life Sciences Max F. Perutz Laboratories, Vienna Director of Cancer Biology Biotechnology Company scientist vaccine research & development Crucell More Science jobs from Drug Discovery EVENT "10th International Congress on Targeted Anticancer Therapies 08.-10.03.12 Amsterdam, Netherlands 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. Recommend SciBX to your library today.   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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