Drug Discovery@nature.com 10 February 2012

TABLE OF CONTENTS 10 February 2012 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement Nature Reviews Cancer POSTER - Proteasome inhibition and cancer therapy Author: Q. Ping Dou This poster highlights recent achievements and progress in targeting the ubiquitin-proteasome degradation pathway for cancer therapy. Access the Poster FREE online! www.nature.com/nrc/posters/proteasome This Poster is freely available thanks to sponsorship from Onyx Pharmaceuticals, Inc.   News Top Drug bests cystic-fibrosis mutation doi:10.1038/482145a First treatment to tackle protein behind the disease wins approval - but only a small fraction of patients will benefit. Full Text Experimental project gives big pharma its youth back doi:10.1038/nature.2012.9979 GlaxoSmithKline's Discovery Performance Units strive to provide the advantages of a smaller company. Full Text Patent Watch: Regeneron and Genentech's VEGF trap dispute settles... and continues doi:10.1038/nrd3667 A round-up of patent-related news, including the outcome of Regeneron’s patent dispute with Genentech over Eylea (aflibercept). Full Text An audience with RuiPing Dong doi:10.1038/nrd3668 RuiPing Dong, head of emerging markets R&D at Merck & Co., discusses the strategy behind the firm's recent US$1.5 billion expansion into China. Full Text Analysis Top Browning fat doi:10.1038/scibx.2012.114 Ember Therapeutics has licensed findings that irisin converts white fat into brown-like fat in mice, and is generating stabilized irisin variants for obesity and type 2 diabetes, while a team that has developed a method for converting human pluripotent stem cells into white and brown adipocytes is collaborating with Roche to screen for molecules that induce or activate brown fat. Full Text Fresh from the Pipeline: Ruxolitinib doi:10.1038/nrd3652 In November 2011, ruxolitinib (Jakafi; Incyte/Novartis), a small-molecule inhibitor of Janus kinases, was approved by the US Food and Drug Administration for the treatment of patients with myelofibrosis. Full Text From the analyst's couch: The neuropathic pain market doi:10.1038/nrd3624 This article discusses the drug pipeline for neuropathic pain, for which the market is forecast to grow by 50% by 2020. Full Text Research Highlights Top Drug delivery: Encapsulation improves therapeutic stem cell action doi:10.1038/nrd3661 Therapeutic stem cells encapsulated in a biodegradable synthetic extracellular matrix show promise in mouse models of human glioblastoma surgical resection. Full Text Anticancer drugs: Keeping one step ahead doi:10.1038/nrd3664 A recent study proposes a new drug combination strategy to target drug-resistant chronic myeloid leukaemia. Full Text Psychiatric disorders: Why two is better than one doi:10.1038/nrn3181 The antidepressant fluoxetine increases synaptic plasticity in the amygdala and thereby facilitates fear erasure through extinction. Full Text Research & Reviews Top Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy doi:10.1038/nrd3628 This article outlines the challenges and opportunities for improving cognition in individuals suffering from psychiatric disorders, whose quality of life can be severely compromised by cognitive deficits. Full Text Targeting MET in cancer: rationale and progress doi:10.1038/nrc3205 Progress in understanding the structure and function of hepatocyte growth factor/scatter factor, MET and associated signalling components has led to the development of blocking antibodies and small-molecule MET kinase inhibitors, as discussed in this Review. Full Text Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates doi:10.1038/nbt.2108 Conjugating drugs to therapeutic antibodies is a promising strategy to increase their therapeutic efficacy. Shen et al. show that the local chemical environment of the conjugation site influences the in vivo stability and efficacy of the modified antibodies. Full Text Gap junction inhibition prevents drug-induced liver toxicity and fulminant hepatic failure doi:10.1038/nbt.2089 Liver toxicity is one of the most common reasons for abandoning new drugs in development or withdrawing approved drugs from the market. Patel et al. show that drug-induced liver injury can be limited in mice by a small-molecule inhibitor of the gap-junctional protein connexin 32. Full Text Drug Discovery JOBS of the week Oncology Group Leader / Project Leader Contract Drug Discovery Organisation Project Development Manager or Business Development Manager (depending on experience) Cancer Research Technology Stem Cells for Drug Discovery and Neural Repair UC Davis Senior Research Scientist � Cancer Abbott Laboratories Associate or Full Professor UIC College of Pharmacy More Science jobs from Drug Discovery EVENT 6th Drug Discovery for Neurodegeneration 12.-14.02.12 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. Full Text Top Advertisement SciBX: Science-Business eXchange is a weekly publication that identifies and analyzes the most important translational research articles from over 40 journals. Find out which papers have real scientific and commercial potential, and why. Recommend SciBX to your library today.   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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