Drug Discovery@nature.com 2 December 2011

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Join in discussions and hot topics shaping the industry.   News Top Success of immunomodulators in MS shifts discovery focus to neuroprotection doi:10.1038/nrd3610 With six immunomodulatory agents in late-stage development for relapsing–remitting multiple sclerosis, this area of the therapeutic space has become highly competitive. Could remyelination therapies that provide neuroprotection be the next frontier? Full Text Quarter-century quest for malaria vaccine shows signs of success doi:10.1038/nrd3611 The long development of RTS,S, the leading malaria vaccine candidate, has yielded preliminary positive Phase III results, and laid a path for future success. Full Text Deal watch: Pfizer deal for selectin inhibitor highlights potential of glycomimetic drugs doi:10.1038/nrd3622 GlycoMimetics has granted Pfizer exclusive worldwide rights to develop and commercialize GMI-1070, a rationally designed glycomimetic inhibitor of E-, L- and P-selectin, for vaso-occlusive crisis associated with sickle cell disease. Full Text Blockbuster drug bows out doi:10.1038/480016a Pharmaceutical industry anxiously struggles to retool as Lipitor patent expires. Full Text Analysis Top Dampening neuroinflammation doi:10.1038/scibx.2011.1254 Researchers have shown that a small molecule inhibitor of monoacylglycerol lipase reduces neuroinflammation in a mouse model of Parkinson's disease, and are studying the compound in other neurodegenerative and neurological diseases. Newco Abide Therapeutics is exercising an option to license these inhibitors. Full Text Crizotinib doi:10.1038/nrd3600 In August 2011, crizotinib (Xalkori; Pfizer), a small-molecule kinase inhibitor, was approved by the US Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer that is anaplastic lymphoma kinase-positive, as detected by an FDA-approved test. Full Text Personalized medicine in oncology: next generation doi:10.1038/nrd3603 This article outlines the challenges, such as clinical trial design, biomarker selection, accurately forecasting sales potential and pricing, that face pharmaceutical companies in the development of targeted drugs. Full Text Research Highlights Top Analgesia: Unravelling epigenetic mechanisms of chronic pain doi:10.1038/nrd3606 Results from a new study suggest that histone deacetylase inhibitors could be used as analgesics to target the development of chronic pain. Full Text Medical devices: A protective stent coating doi:10.1038/nrd3604 Researchers have shown that coating stents with cathelicidin, an antimicrobial peptide released from neutrophils, could represent a novel strategy for preventing restenosis. Full Text Therapeutics: Another tool in the BCR–ABL kit? doi:10.1038/nrc3173 Inhibiting an interaction between the SH2 and kinase domains of BCR–ABL, which facilitates kinase activation, prevents leukaemogenesis in mice and can restore sensitivity to tyrosine kinase inhibitors. Full Text Research & Reviews Top Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets doi:10.1038/nrd3599 This article summarizes the evidence for the participation of CCN matricellular proteins in disease pathologies, explores their potential as diagnostic markers and therapeutic targets, and outlines various strategies to target these proteins. Full Text MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy doi:10.1038/nrc3166 In addition to highlighting the use of mouse models to understand the roles of miRNAs in cancer and metastasis, this article reviews the recent literature regarding the transition of these master regulators into clinical settings both as direct cancer therapeutics and as tools to sensitize tumours to traditional chemotherapeutics. Full Text The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis doi:10.1038/nm.2579 Preliminary evidence indicates that the drug dexpramipexole may have clinical activity in a small placebo-controlled trial in patients with the neurodegenerative disease amyotrophic lateral sclerosis. Full Text RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E) doi:10.1038/nature10662 Researchers have identified a novel mechanism of acquired resistance to RAF inhibitors in patients: expression of splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner. Full Text Drug Discovery JOBS of the week Postdoctoral positions in Stem Cells and Immunology University of Connecticut Editorial Manager, PLoS ONE Public Library of Science (PLoS) Assistant or Associate professor University of Texas Medical School at Houston Postdoctoral Position in Stem Cell Biology Children's Hospital Oakland Research Institute (CHORI) Clinical Trial Manager The Instute of Cancer Research More Science jobs from Drug Discovery EVENT International Conference on Drug Therapy in TB Infection 06.-07.01.12 Edinburgh, UK 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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