Drug Discovery@nature.com 3 February 2012

TABLE OF CONTENTS 3 February 2012 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement Miami 2012 Winter Symposium: Nanotechnology in Biomedicine February 26-29, 2012 • Miami, FL, USA The 45th Miami Winter Symposium will bring together leaders in the field to discuss breakthroughs in new nanomaterials and the challenges in translating these materials into products for the clinic and laboratory. For more information and to register, visit: www.nature.com/natureconferences/miami/mws2012   News Top 2011 FDA drug approvals doi:10.1038/nrd3657 The US Food and Drug Administration approved 30 new therapeutics last year, including 11 first-in-class agents. Full Text Informed consent on trial doi:10.1038/482016a Lengthy, complicated documents leave many clinical-trial participants in the dark about the risks they face. Full Text Trial watch: BTK inhibitor shows positive results in B cell malignancies doi:10.1038/nrd3656 Trial data indicated that the Bruton's tyrosine kinase inhibitor PCI-32765 — which is at the centre of a deal worth up to US$975 million between its developer Pharmacyclics and Janssen Biotech — is effective in treating several types of B cell lymphoma. Full Text Deal watch: Abbott boosts investment in NRF2 activators for reducing oxidative stress doi:10.1038/nrd3655 Abbott has agreed to pay US$400 million upfront to Reata Pharmaceuticals in a deal to develop oral antioxidant inflammation modulators with potential applications in cardiovascular disease, neurodegenerative disorders and immunology. Full Text Analysis Top Macrocycles by the trillions doi:10.1038/scibx.2012.87 Japanese researchers have developed a method for creating large libraries of N-methylated peptide macrocycles. PeptiDream Inc. has exclusively licensed the technology and set up collaborations with six pharmas. 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 Scientist, Biopharmacology Eisai Europe Ltd Principal Investigators for National New Drug R&D Projects IPT Stem Cells for Drug Discovery and Neural Repair UC Davis Associate Scientist, Toxicology Genentech Scientist, Bioinformatics Takeda Pharmaceutical Company Ltd. More Science jobs from Drug Discovery EVENT Resolving Inflammation: Mechanisms and Drug Discovery 01.-03.04.12 Oxford, UK 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. 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