Drug Discovery@nature.com 13 December 2013

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ReichertSPR.com Nature Reviews Drug Discovery is on Twitter Advertisement Nature Biotechnology FREE POSTER  Antibody-drug conjugates for cancer therapy  Several antibody-drug conjugates have been approved for clinical use in a variety of solid and hematological tumors, with many more in human testing. Nature Biotechnology presents a poster by Dario Neri of ETH Zurich describing the various linker strategies, cytotoxic payloads and mechanisms/sites of action of these drugs. Made available with the generous support of  Millennium: The Takeda Oncology Company and Seattle Genetics   News Top Project ranks billions of drug interactions doi:10.1038/503449a Drugable.com predicts mechanisms through computation. Full Text Personalized cancer treatments suffer setback doi:10.1038/nature.2013.14238 Analysis suggests studies give conflicting answers about whether cancers respond to targeted drugs. Full Text NIH denies march-in rights on Norvir patent doi:10.1038/nrd4198 The US National Institutes of Health (NIH) has refused to override AbbVie's patents on the HIV drug Norvir (ritonavir) under so-called march-in rights, which means that the cost of Norvir in the US will remain higher than in several other high-income countries. Full Text An Audience With...Charles Hugh-Jones doi:10.1038/nrd4190 Charles Hugh-Jones, Chief Medical Officer in North America at Sanofi, discusses Project Data Sphere, a new collaborative platform for sharing cancer clinical trial data. Full Text Analysis Top Targeting fibrotic integrin doi:10.1038/scibx.2013.1308 An international team of researchers has shown that the myofibroblast-expressed integrin αv subunit drives fibrosis and that a small molecule integrin αV antagonist from Antegrin Therapeutics can attenuate the process in mice. The biotech is developing an improved version of the compound for pulmonary fibrosis. Full Text Does size matter in R&D productivity? If not, what does? doi:10.1038/nrd4164 This analysis of factors that affect the likelihood of success in drug research and development (R&D) indicates that scientific acumen and good judgment – particularly with regard to the early termination of less viable drug candidates – are crucial. Full Text Research Highlights Top Autoimmune disease: Parkinson's drug promotes myelin repair doi:10.1038/nrd4181 A study in Nature reports that a drug currently approved for the treatment of Parkinson's disease promotes neuronal myelination and decreases the clinical severity of MS in mouse models. Full Text Neurological disorders: Chloride extrusion alleviates neuropathic pain doi:10.1038/nrd4183 Activators of the potassium-chloride co-transporter KCC2 show promising oral efficacy in a rat model of neuropathic pain. Full Text Bone disorders: Targeting NOX4 knocks down osteoporosis doi:10.1038/nrd4182 NADPH oxidase 4 (NOX4) – an enzyme that is involved in the production of reactive oxygen species – could be a therapeutic target for disorders characterized by bone loss, such as osteoporosis. Full Text Advertisement Drug delivery: enabling technology for drug discovery and development. iPRECIO™ Micro Infusion Pump: programmable, refillable, and implantable (open access) In this technology report, Tsung Tan and colleagues describe five different iPRECIO™ applications in detail with references to the original work where the implantable, refillable, and programmable benefits are demonstrated with their different end-points. Read more high-quality articles from Frontiers in Pharmacology   Research & Reviews Top Modulation of oxidative stress as an anticancer strategy doi:10.1038/nrd4002 The role of ROS in cancer cells is controversial as they can have both pro-tumorigenic and antitumorigenic properties. This article discusses recent findings that cancer cells upregulate antioxidant pathways to counteract ROS, and explores the potential of anticancer strategies that target the antioxidant capacity of tumour cells. Full Text Chemical predictive modelling to improve compound quality doi:10.1038/nrd4128 The potency, selectivity and pharmacokinetic characteristics of small-molecule compounds are some of the key factors influencing their chances of success in clinical trials. This article discusses the application of computational methods, particularly quantitative structure-activity relationships, in guiding the selection of higher-quality drug candidates. Full Text bHLH–PAS proteins in cancer doi:10.1038/nrc3621 Mammalian basic HLH (helix-loop-helix)-PER-ARNT-SIM (bHLH-PAS) proteins are heterodimeric transcription factors. Recently determined structures of their PAS domains and successful small-molecule screening programmes are now providing new opportunities to discover selective agonists and antagonists directed against this multitasking family of transcription factors. Full Text Antimalarial drug discovery — approaches and progress towards new medicines doi:10.1038/nrmicro3138 Current antimalarial therapy heavily relies on artemisinins, a drug class that only targets the blood stages of the parasite and which is increasingly feared to elicit drug resistance. This article discusses the approaches used to develop novel drugs that are active against different life cycle stages with the ultimate aim of eliminating malaria. Full Text Drug Discovery JOBS of the week Research Assistant, Controlled Drug Release From Biodegradable And Biocompatible Platforms Waterford Institute of Technology Staff Scientist - Aerosol Drug Delivery Wyss Institute for Biologically Inspired Engineering PhD students and postdoctoral researchers positions in Drug Discovery Shanghai Jiao Tong University Imaging of control drug release materials using hyperpolarised 129Xe MRI The University of Nottingham Postdoctoral Researcher in Biomaterials and Drug Delivery Vanderbilt University, Department of Chemical and Biomolecular Engineering More Science jobs from Drug Discovery EVENT 6th International Conference on Drug Discovery and Therapy 10.02.14 Dubai 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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