Drug Discovery@nature.com 23 December 2011

TABLE OF CONTENTS 23 December 2011 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement Nature Reviews Neuroscience FOCUS ON ADDICTION Read for FREE online at: www.nature.com/nrn/focus/addiction Produced with support from National Institute on Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) National Institutes of Health U.S. Department of Health & Human Services   News Top New startup models emerge as investor landscape shifts doi:10.1038/nbt1211-1066c Venture capital firms are finding creative ways of overcoming the challenging timelines and restricted exits for early-stage life sciences investments. Full Text Trial networks move beyond single-disease strategies doi:10.1038/nm1211-1525 Individual institutes are aiming to take a more interdisciplinary, multidisease approach to their clinical extramural programs. Full Text Newsmaker: Zafgen doi:10.1038/nbt1211-1068 Zafgen hopes that small-molecule targeting of methionine aminopeptidase 2 (MetAP2), an enzyme originally associated with tumor angiogenesis, will lead to a new anti-obesity drug. Full Text Conflicts of interest go online doi:10.1038/nbt1211-1058 The European Medicines Agency (EMA) has recently launched a new database aimed at increasing the transparency of expert advisors' financial ties to industry. Full Text Analysis Top Splicing out BRAF′s resistance doi:10.1038/scibx.2011.1340 The discovery of a mechanism by which melanomas expressing mutant BRAF acquire resistance to targeted drugs gives companies a new resistance mechanism to screen against in the design of next-generation BRAF inhibitors and furthers the case for combining Zelboraf with downstream kinase 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 Research Fellow Medical University of South Carolina (USA) Postdoctoral Research Associate - Cancer Therapy Scripps Florida Senior Scientist of antibody drug discovery GenScript USA Inc. Chair in Medicinal Chemistry University of London Post-Doctoral (WW) - Target Identification and Drug Discovery - Immunobiology and Cancer Research Program (W Wang) Oklahoma Medical Research Foundation (OMRF) More Science jobs from Drug Discovery EVENT Drug Discovery for Protozoan Parasites (J1) / Fungal Pathogens: From Basic Biology to Drug Discovery (J2) 15.-20.01.12 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. Full Text Top Advertisement Nature Immunology presents a webcast series on Current Controversies Webcasts now available free on demand on the following topics: Lineage Differentiation HIV Vaccines Human Immunology Sponsored by:   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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