Drug Discovery@nature.com 25 May 2012

TABLE OF CONTENTS 25 May 2012 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement Nature Neuroscience FOCUS ON SOCIAL NEUROSCIENCE This Focus discusses how the brain implements social processes and behavior, and how these processes are in turn modified by the brain, to influence things ranging from physical and mental health to the punishment of deviation from social norms. Read this Focus online: www.nature.com/neuro/focus/socialneuroscience   News Top US government sets out Alzheimer’s plan doi:10.1038/485426a Health-agency budget windfall includes funding for two promising clinical trials. Full Text Failings exposed at India’s drug regulator doi:10.1038/nature.2012.10668 Inadequate testing and insufficient staffing plague the granting of pharmaceutical licences. Full Text JAK pot for Galapagos doi:10.1038/nbt0512-374 In late February, biotech Galapagos entered a pact with Abbott Laboratories worth $1.35 billion over rights to the experimental rheumatoid arthritis drug GLPG0634, a small-molecule Janus kinase 1 inhibitor. Full Text New biologic drugs get under the skin of psoriasis doi:10.1038/nm0512-638 New results on the clinical efficacy of two experimental psoriasis medications are creating a buzz among those who study and treat the skin disease. Full Text Analysis Top Eyeing the inflammasome doi:10.1038/scibx.2012.511 Two academic teams have shown that targeting the inflammasome reduces retinal damage in mouse models of age-related macular degeneration; one approach has been licensed to iVeena Pharmaceuticals Inc., while the other team is developing their own gene therapy. Full Text Fresh from the Pipeline: Ivacaftor doi:10.1038/nrd3723 First disease-modifying drug approved in the United States for the treatment of cystic fibrosis in patients with a specific mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator. Full Text From the analyst's couch: Drug development risk and the cost of capital doi:10.1038/nrd3722 This article analyses the relationship between risk and the cost of capital for projects in different stages of drug development and describes a framework that could improve portfolio optimization strategies. Full Text Research Highlights Top Neurodegenerative disease: The stress of misfolding doi:10.1038/nrd3731 Two studies provide evidence that α-synuclein-induced endoplasmic reticulum (ER) stress has a crucial role in promoting neurodegeneration in α-synucleinopathies, and that targeting chronic ER stress may represent a plausible target for future therapies. Full Text Cancer genomics: Constructing a 'cancerpaedia' doi:10.1038/nrd3730 Two recent papers published in Nature report on genomic changes in cancer cell lines that indicate sensitivity to targeted drugs. Full Text Mouse models: Of mice and men doi:10.1038/nrc3270 A clinical trial in mice with lung cancer indicates the likely efficacy of the MEK inhibitor selumetinib in a current ongoing human clinical trial. Full Text Research & Reviews Top Epigenetic protein families: a new frontier for drug discovery doi:10.1038/nrd3674 In this article, the authors review the protein families that mediate epigenetic signalling through histone acetylation and methylation, and highlight progress in the pharmacological modulation of each class of proteins. Full Text Intra-tumour heterogeneity: a looking glass for cancer? doi:10.1038/nrc3261 This Review outlines both genetic and non-genetic causes of phenotypic heterogeneity of tumour cells and the implications of intra-tumour heterogeneity in diagnostics and the development of therapeutic resistance. Full Text The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma doi:10.1038/nature11114 A transposon-mediated insertional mutagenesis screen reveals inactivation of the X-linked deubiquitinase gene Usp9x in over 50% of pancreatic ductal adenocarcinomas, suggesting Usp9x has prognostic and therapeutic relevance for this disease. Full Text A selective inhibitor reveals PI3Kγ dependence of TH17 cell differentiation doi:10.1038/nchembio.957 A chemoproteomic approach adapted for high-throughput screening leads to the identification of a selective PI3Kγ inhibitor. Application of this inhibitor in human and mouse cellular models reinforces selective inhibition of PI3Kγ as a potential treatment for inflammatory and autoimmune diseases. Full Text Drug Discovery JOBS of the week Fully Funded Studentship: Host-guest interactions in advanced drug delivery systems: NMR studies University of East Anglia (UEA) Post-Doctoral Researcher in Drug Delivery and Formulation Univeristy College Cork Postdoctoral Research Officer in Nanoparticles for Drug Release to the Brain University of Bath Postdoctoral Fellow in Computational Structure-Based Drug Design Mount Sinai School of Medicine (Zhou Lab) Director, Center for Drug Delivery and Nanomedicine (CDDN) University of Nebraska College of Pharmacy More Science jobs from Drug Discovery EVENT ADME, PK/TK, and Drug Metabolism in Drug Discovery and Development 17.-19.09.12 Dublin, Ireland 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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