Drug Discovery@nature.com 12 September 2014

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TABLE OF CONTENTS 12 September 2014 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement Nature Reviews Rheumatology  FOCUS ON VASCULITIS  Specially commissioned articles outline the latest research in the field of vasculitis, covering topics including vasculature development, and vasculitis pathogenesis and treatment. Produced with support from  Genentech, a member of the Roche group      News Top First PD-1 inhibitor breezes across finish line doi:10.1038/nbt0914-847 Ono Pharmaceutical and partner Bristol-Myers Squibb achieved a world first by gaining approval in Japan for Opdivo (nivolumab), a fully human IgG4 antibody that inhibits programmed death 1, for treating unresectable melanoma. Full Text Sanofi to propel inhalable insulin Afrezza into market doi:10.1038/nbt0914-851a MannKind has found a deep-pocketed business partner to market its inhaled insulin therapy, Afrezza, which was approved in late June as a prandial insulin to improve glycemic control in individuals with either type 1 or type 2 diabetes. Full Text An audience with… Bob More doi:10.1038/nrd4421 Bob More, venture capitalist with the Bill and Melinda Gates Foundation, discusses the challenges of aligning financial and philanthropic interests. Full Text Small biotech steers HDAC inhibitor to clinic doi:10.1038/nbt0914-853 The approval of the histone deacetylase (HDAC) inhibitor Beleodaq (belinostat) marks the third HDAC inhibitor to gain registration in the US and the first in almost five years—all for treating rare T-cell lymphomas. Full Text Analysis Top The HIV pipeline doi:10.1038/nrd4364 This article provides an overview of the diverse anti-HIV agents in development, including combination therapies, and an analysis of the market for current and future HIV treatments. Full Text Selectively splicing SMN2 doi:10.1038/scibx.2014.1001 A three-way collaboration between PTC, Roche and the Spinal Muscular Atrophy Foundation has resulted in orally available, blood brain barrier–penetrant, selective small molecule modulators of SMN2 that are advancing in the clinic to treat spinal muscular atrophy. Full Text Research Highlights Top Epilepsy: Endocannabinoid metabolism offers handle to dampen down excitability doi:10.1038/nrd4418 Targeting the serine hydrolase α/β-hydrolase domain 6, which is involved in endocannabinoid metabolism, can protect against seizures in mouse models of epilepsy. Full Text Obesity and diabetes: FGF1 goes long to tackle diabetes doi:10.1038/nrd4419 Subcutaneous delivery of fibroblast growth factor 1 (FGF1) confers novel insulin-sensitizing properties to this molecule in diabetic mice while avoiding many of the side effects associated with current antidiabetic drugs. Full Text Neurodevelopmental disorders: Righting Rett syndrome with IGF1 doi:10.1038/nrd4417 Two papers show that treatment with insulin-like growth factor 1 (IGF1) and/or the β2-adrenergic receptor agonist clenbuterol can alleviate symptoms in mouse models of Rett syndrome. Full Text Research & Reviews Top Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies doi:10.1038/nrd4363 Biological drugs offer high specificity and potency, but their formulation and delivery pose substantial challenges. This article highlights recent advances in formulation strategies, describes current and emerging delivery routes and reviews the potential of targeted and intracellular delivery of biologics. Full Text Strategies to improve drug development for sepsis doi:10.1038/nrd4368 Despite numerous clinical trials, no specific therapeutic agent is currently approved for sepsis. Here, Fink and Warren consider potential reasons for such failures and suggest possible strategies to overcome ongoing challenges, such as improving clinical trial design. Full Text Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders doi:10.1038/nrd4360 Histone deacetylases (HDACs) are a class of epigenetic enzymes that remove acetyl groups from lysine residues on histones and other proteins. In this review, the authors highlight the role of HDACs in cancer, neurological diseases and immune disorders, and discuss the development of small-molecule inhibitors. Full Text Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders doi:10.1038/nrd4308 Compared to traditional drugs that target the orthosteric ligand-binding site of GPCRs, allosteric modulators have the potential to achieve greater subtype selectivity and allow the normal function of endogenous ligands to be preserved. Conn and colleagues reflect on the key principles for successful optimization of GPCR allosteric modulators. Full Text Drug Discovery JOBS of the week Non-invasive diagnosis and drug screening in neurological infections KU Leuven PhD scholarship in Drug Delivery Technical University of Denmark (DTU) Head of Drug and RNAi Screening Platform UCLA Professorship (W2) "Phospholipids in Drug Development" Friedrich Schiller University Jena Post-Doc position in electro-spinning -- scaffolding and drug delivery for regenerative medicine applications Center for Nanomedicine and Tissue Engineering - A.O. Niguarda Ca' Granda More Science jobs from Drug Discovery EVENT 6th Annual Global Drug Delivery & Formulation Summit 09.02.15 Dusseldorf, Germany 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 Cell Death & Disease: submit your forthcoming manuscript  Ensure wide visibility and global reach for your next piece of research - find out more about the benefits of submitting to Cell Death & Disease   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. 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