Drug Discovery@nature.com 12 October 2012

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Nature Reviews Drug Discovery is on Twitter Advertisement Nature and Nature Reviews Cancer WEB FOCUS: CANCER METABOLISM A renaissance in the field of cancer metabolism has demonstrated links between oncogenic pathways and the mechanistic basis of tumour cell metabolism. This joint Nature and Nature Reviews Cancer Web Focus highlights recent progress in the field and the promise of therapeutics based on interfering with metabolic pathways. Access the Web Focus at: www.nature.com/focus/cancermetabolism   News Top Companies wager high on CD38-targeting drugs for blood cancer doi:10.1038/nm1012-1446a This article looks at the rise of drugs targeting CD38, a protein found on the surface of some cells which become malignant in certain cancers. Full Text Early-stage therapies target surgery-induced erectile dysfunction doi:10.1038/nm1012-1444 A new generation of neuroprotective drugs or cell therapies given around the time of surgery could one day protect sexual function in prostate cancer survivors. Full Text SGLT2 inhibitors race to enter type-2 diabetes market doi:10.1038/nbt1012-899 Canagliflozin is in pole position to become the first sodium-glucose co-transporter 2 inhibitor to gain a US approval in type-2 diabetes, while a rival compound, Forxiga, is likely to gain approval in Europe. Full Text Novel Indian clotbuster doi:10.1038/nbt1012-903b Clot-specific streptokinase, a new thrombolytic treatment discovered in India, is poised to enter clinical trials. The home-grown clot-dissolving therapeutic could become the first innovative compound from an Indian public institute jointly developed with a US company. Full Text Analysis Top Slipping past P glycoprotein doi:10.1038/scibx.2012.1019 NIH researchers have shown that sphingosine 1-phosphate receptor agonists could enhance drug delivery to the brain. The group is evaluating the approach for improving drug delivery to brain tumors. Full Text From the analyst's couch: Autism spectrum disorders doi:10.1038/nrd3771 This analysis looks at the increasing number of candidates in the pipeline for autism spectrum disorders, reflecting the increasing prevalence of autism and the growing interest in finding novel treatments. Full Text Research Highlights Top Neurodegenerative diseases: Anti-epileptic drug shows benefit in AD mouse model doi:10.1038/nrd3850 Using a mouse model engineered to overexpress human amyloid precursor protein and amyloid-β, researchers have shown that cognitive and synaptic deficits are caused by aberrant neuronal network activity, and that this can be improved with an anti-epileptic drug. Full Text Vaccines: Self-amplifying RNA in lipid nanoparticles: a next-generation vaccine? doi:10.1038/nrd3854 A new vaccine platform based on self-amplifying RNA encapsulated in synthetic lipid nanoparticles overcomes some of the limitations of earlier nucleic-acid-based approaches. Full Text Metabolic disorders: Safe cannabinoid receptor modulators in sight? doi:10.1038/nrd3851 A peripherally selective CB1R inverse agonist can safely and effectively reduce body weight in a mouse model of obesity, without affecting behaviour. Full Text Research & Reviews Top Targeting the TGFβ signalling pathway in disease doi:10.1038/nrd3810 This Review considers why the TGFβ signalling pathway is a drug target, the potential clinical applications of TGFβ inhibition, the issues arising with anti-TGFβ therapy and how these might be tackled. Full Text Targeting cells in chronic inflammation doi:10.1038/nrd3794 This Review focuses on the current knowledge of the IL-17–TH17 cell pathway to better understand the positive as well as potential negative consequences of targeting them. Full Text Naratriptan mitigates CGRP1-associated motor neuron degeneration caused by an expanded polyglutamine repeat tract doi:10.1038/nm.2932 Researchers describe a molecular cascade whereby mutant androgen receptor upregulates CGRP in neuronal cells, promoting JNK activation and degeneration. The 5-HT1B/1D receptor agonist naratriptan decreases CGRP expression and improves motor performance in a mouse model of SBMA. Full Text Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function doi:10.1038/nchembio.1081 Researchers propose that compounds binding a newly discovered allosteric site of the hepatitis C virus’s NS3 protein may inhibit its function, and thus represent a new class of direct-acting antiviral agents. Full Text Drug Discovery JOBS of the week Postdoc in drug delivery, nanotechnology, and biomaterials University of Michigan Drug Analyst - Citeline Pharmaceutical Intelligence Citeline Drug Discovery Programme - Head of Biology Beatson Institute for Cancer Research Postdoctoral Fellowship in Synthetic Cell-Based Screening / Microfluidics / Drug Discovery The Scripps Research Institute (TSRI) Postdoctoral in Chemical Biology for Drug Discovery in Parasitology GlaxoSmithKline More Science jobs from Drug Discovery EVENT 7th World Congress on Prevention of Diabetes and its Complications 12.-14.11.12 Madrid, Spain 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. 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