Drug Discovery@nature.com 18 May 2012

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Access the Web Focus at: www.nature.com/focus/cancermetabolism   News Top Fifth time's the charm for infant respiratory distress drug doi:10.1038/nbt0512-380c After four previous submissions over the past eight years, the US Food and Drug Administration finally approved Surfaxin (lucinactant), manufactured by Discovery Labs in Warrington, Pennsylvania, for the treatment of respiratory distress in preterm infants. Full Text Patent watch: Drug dosage patent ban casts doubt on diagnostics doi:10.1038/nrd3735 A round-up of patent-related news, including the decision by the US Supreme Court that methods of determining therapeutic doses of a drug, based on the measurement of drug metabolite levels, are not eligible for patent protection. Full Text Hypoxia-activated prodrugs forge ahead in cancer doi:10.1038/nbt0512-381 After a string of high-profile failures, hypoxia-inducible prodrugs are undergoing a revival, with two compounds showing promising results in clinical trials against pancreatic cancer and leukemia. Full Text Biologic drugs set to top 2012 sales doi:10.1038/nm0512-636a Three biologic medicines initially developed to treat rheumatoid arthritis are on track to top the sales charts this year. Full Text Analysis Top A mind for precompetitive collaboration doi:10.1038/scibx.2012.483 Although pharmas are cutting back on internal neuroscience R&D programs, the number of precompetitive consortia backed by industry continues to rise. 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 Observational, prospective study about the incidence of adverse drug effects in patients with drug-resistence epilepsy Università degli Studi di Firenze- Dipartimento di Scienze Neurologiche e Psichiatriche Postdoctoral Fellow in Computational Structure-Based Drug Design Mount Sinai School of Medicine (Zhou Lab) Sr. Programmer Analyst, Drug Safety Genentech Director, Center for Drug Delivery and Nanomedicine (CDDN) University of Nebraska College of Pharmacy PhD Positions available in nanomaterials, intelligent nanomembranes, foldable devices and drug delivery Monash University, Alfred Hospital More Science jobs from Drug Discovery EVENT 6th Drug Discovery & Development Japan 2012 11.-14.06.12 Tokyo, Japan 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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