Drug Discovery@nature.com 09 November 2012

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Submit your next research to Scientific Reports *mean time for papers published in September 2012   News Top Cholesterol-lowering blockbuster candidates speed into Phase III trials doi:10.1038/nrd3879 Less than a decade on from genetic studies indicating the potential of PCSK9 as a target to affect cholesterol metabolism, two PCSK9 inhibitors are moving into late-stage development. Full Text New class of kinase inhibitors poised to join the anticancer arsenal doi:10.1038/nrd3880 Long-standing efforts to develop drugs that target MEKs could soon come to fruition, moving the frontier to how best to combine them with other cancer therapies. Full Text Deal watch: J&J and Genmab deal to push forward CD38 as a blood cancer target doi:10.1038/nrd3890 J&J has finalized a deal to in-license daratumumab, an anti-CD38 monoclonal antibody that is in early-stage development for multiple myeloma by the Danish biotech company Genmab. Full Text Deal watch: 'Big data' deal for diabetes clinical trial modelling doi:10.1038/nrd3891 Data analytics company GNS Healthcare and the contract research organization Covance have entered into a deal to develop predictive models of clinical trials. Full Text Analysis Top Melanoma's hidden act doi:10.1038/scibx.2012.1100 Melanoma cells can acquire resistance to adoptive T cell transfer therapies by dedifferentiating themselves to hide antigens. Researchers are trying to circumvent this resistance mechanism to improve treatment responses for T cell therapy protocols. Full Text From the analyst's couch: Wet AMD market doi:10.1038/nrd3790 This analysis looks at the currently available therapies for age-related macular degeneration and at the emerging treatments that might offer more convenient and cost-effective options. Full Text Research Highlights Top Alzheimer's Disease: JNK3 as new target in AD? doi:10.1038/nrd3876 Researchers have shown that Alzheimer’s disease is under tight control by JNK3, through a complex loop that drives the production of the neurotoxic peptide Aβ42. JNK3 deletion alleviated symptoms in a mouse model. Full Text Metabolic disorders: New avenue to AMPK activation doi:10.1038/nrd3872 Researchers have identified a novel small-molecule AMPK activator that, through a mechanism involving NUR77, reduces blood glucose and alleviates insulin resistance in mouse models of diabetes. Full Text G Protein-coupled receptors: Expanding the detection of GPCR activation doi:10.1038/nrd3874 A new high-throughput assay overcomes some limitations of previous assays, allowing the accurate detection of a wider range of GPCRs. Full Text Research & Reviews Top Structure and mechanism of a bacterial sodium-dependent dicarboxylate transporter doi:10.1038/nature11542 This study provides insights into the NaCT protein, including the identification of the substrate-binding motifs. This may aid the design of agents that target this protein to treat obesity, diabetes and cardiovascular diseases. Full Text Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways doi:10.1038/nm.2962 The administration of LNFPIII, an immunomodulatory glycan found in human milk and on parasitic helminths, improves glucose tolerance and insulin sensitivity in diet-induced obese mice. Full Text MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles doi:10.1038/nrd3864 This Review focuses on the pharmacokinetic and pharmacodynamic properties of current miRNA inhibitor designs and their relevance to cardiovascular indications, and evaluates the opportunities and obstacles associated with this new therapeutic modality. Full Text The spliceosome as a target of novel antitumour drugs doi:10.1038/nrd3823 This Review looks at drugs that target the alternative splicing of genes that are important for cancer progression, and at how an understanding of the molecular mechanisms of these may open new perspectives for novel antitumour therapies. Full Text Drug Discovery JOBS of the week Director Research and Drug Development Children's Tumor Foundation Scientist / Sr Scientist � Oncology Drug Discovery H3 Biomedicine Postdoc in drug delivery, nanotechnology, and biomaterials University of Michigan 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 More Science jobs from Drug Discovery EVENT Systems Biology Approaches to Drug Discovery: Single Gene Targeting is Not Enough 11.12.12 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. 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