Nature Reviews Drug Discovery contents January 2013 Volume 12 Number 1 pp 1-82

TABLE OF CONTENTS
January 2013 Volume 12 Number 1
Impact Factor 29.008 *	In this issue Comment News and Analysis Research Highlights Perspectives Analysis Reviews Also this month  Featured article: Objective assessment of cancer genes for drug discovery Mishal N. Patel, Mark D. Halling-Brown, Joseph E. Tym, Paul Workman & Bissan Al-Lazikani
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Nature Reprint Collection on Epigenetics www.nature.com/reprintcollections/epigenetics This collection of articles focuses on histone methylation, its links to human disease and the development of chemical modulators of histone methylation states as leads for chromatin-targeted drug discovery. Produced exclusively with support from:
In this issue p1 | doi:10.1038/nrd3920 Full Text
Comment: Pharmacogenetic tests: the need for a level playing field Munir Pirmohamed & Dyfrig A. Hughes p3 | doi:10.1038/nrd3921 Abstract | Full Text | PDF
NEWS AND ANALYSIS		Top
Fragment-based lead discovery grows up Monya Baker p5 | doi:10.1038/nrd3926 With multiple drug candidates in the clinic that originated from fragment-based lead discovery, the approach of starting small has become big. PDF
2012 in reflection Man Tsuey Tse & Peter Kirkpatrick p8 | doi:10.1038/nrd3927 Last year saw the largest loss of revenue yet from major drugs due to patent expiries, but a continuation of 2011's higher level of drug approvals and new initiatives to address R&D challenges provide hope for the future. PDF
BIOBUSINESS BRIEFS Market watch: Upcoming market catalysts in Q1 2013 Edny Inui p12 | doi:10.1038/nrd3928 PDF
BIOBUSINESS BRIEFS Trial watch: Enzyme replacement success in Phase III trial for rare metabolic disorder Sarah Crunkhorn p12 | doi:10.1038/nrd3929 PDF
PATENT WATCH Dangling from the patent cliff Charlotte Harrison p14 | doi:10.1038/nrd3924 PDF
AN AUDIENCE WITH Luca Santarelli p14 | doi:10.1038/nrd3925 Roche is one of the few pharmaceutical companies that has stayed firmly committed to research and development for central nervous system disorders. Here, Luca Santarelli, Senior Vice President and Head of Neuroscience Research and Early development, discusses why. PDF
FROM THE ANALYST'S COUCH Alzheimer's disease market: hope deferred Zelicia Gerald & Waldemar Ockert p19 | doi:10.1038/nrd3922 The last few months have seen a flurry of trial results for investigational agents in Alzheimer's disease (AD). This analysis investigates the different categories of developmental drugs in AD, and provides an outlook to the future of the AD market. PDF
RESEARCH HIGHLIGHTS Top Neurological disorders: Targeting translation in autism p21 | doi:10.1038/nrd3915 PDF Immunomodulators: Particulate promotion of tolerance p22 | doi:10.1038/nrd3916 PDF Gene therapy: Suppressing seizures p22 | doi:10.1038/nrd3918 PDF Lung disorders: A new model and modulator of pulmonary oedema p23 | doi:10.1038/nrd3917 PDF Immunotherapy: Immunological bullets against Alzheimer's disease p24 | doi:10.1038/nrd3919 PDF IN BRIEF G protein-coupled receptors: An endogenous allosteric cannabinoid modulator | RNA interference: Reducing off-target effects of shRNA | Obesity and diabetes: Tissue targeting of oestrogen | Drug delivery: Injectable biomaterials PDF Drug Discovery JOBS of the week PhD Position: Functionalized Inorganic Materials for Water Remediation and Drug Delivery University of Southern Denmark, Department of Physics, Chemistry and Pharmacy More Science jobs from Drug Discovery EVENT 5th International conference on drug discovery and therapy 18.-21.02.13 Dubai, UAE More science events from
PERSPECTIVES		Top
OPINION The GPCR Network: a large-scale collaboration to determine human GPCR structure and function Raymond C. Stevens, Vadim Cherezov, Vsevolod Katritch, Ruben Abagyan, Peter Kuhn, Hugh Rosen & Kurt Wüthrich p25 | doi:10.1038/nrd3859 The GPCR Network was established in 2010 with the aim of structurally characterizing 15-25 representative human G protein-coupled receptors (GPCRs) within 5 years; so far, more than eight have been determined. Here, Stevens and colleagues provide an overview of this collaborative effort and the challenges remaining in gaining detailed insights into the structure-function relationships of this receptor superfamily. Abstract | Full Text | PDF
ANALYSIS		Top
Objective assessment of cancer genes for drug discovery Mishal N. Patel, Mark D. Halling-Brown, Joseph E. Tym, Paul Workman & Bissan Al-Lazikani p35 | doi:10.1038/nrd3913 Effectively selecting therapeutic targets from the sizeable lists that are emerging from large-scale multi-omics initiatives is a key challenge in drug discovery. This article describes an objective, systematic computational assessment of biological and chemical space that can be applied to any human gene set to prioritize targets for further evaluation, and demonstrates its use on a set of 479 cancer-associated genes to identify new opportunities for drug discovery and repurposing. Abstract | Full Text | PDF | Supplementary information
REVIEWS		Top
Therapeutic opportunities for manipulating TReg cells in autoimmunity and cancer Harald von Boehmer & Carolin Daniel p51 | doi:10.1038/nrd3683 Regulatory T (TReg) cells are essential mediators of immune homeostasis. They are attractive targets for steering the immune system in desired directions — arming it to destroy cancer cells or downregulating it in autoimmunity. In this Review, Daniel and von Boehmer discuss how molecular insights into the generation and proliferation of these cells can be exploited for new therapeutic approaches. Abstract | Full Text | PDF
Kynurenines in the CNS: recent advances and new questions László Vécsei, Levente Szalárdy, Ferenc Fülöp & József Toldi p64 | doi:10.1038/nrd3793 Most metabolites of the kynurenine pathway — which metabolizes tryptophan — are neuroactive. This Review describes the role of the kynurenine pathway in the pathology of Huntington's disease, migraine and multiple sclerosis, and highlights the most promising compounds that could be of therapeutic value. Abstract | Full Text | PDF | Supplementary information
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*2011 Journal Citation Report (Thomson Reuters, 2012)

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