Nature Reviews Drug Discovery contents April 2018 Volume 17 Number 4 pp 225-299

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TABLE OF CONTENTS
April 2018 Volume 17 Number 4		Advertisement
2016 2-year Impact Factor 57.000 Journal Metrics 2-year Median 38	In this issue Comment News and Analysis Research Highlights Reviews Correspondence   Also this month  Featured article: mRNA vaccines — a new era in vaccinology Norbert Pardi, Michael J. Hogan, Frederick W. Porter & Drew Weissman	Ionis Pharmaceuticals, Nature Structural and Molecular Biology & Nature Biotechnology present: RNA at the Bench & Bedside October 8-10, La Jolla, USA RNA therapeutics is poised to deliver major advances. This conference will discuss the many roles of RNAs and the translation of basic science into new therapies. It will address the opportunities, current status and future of this exciting field.
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Harrington drug discovery research grants - awards up to $700,000 Harrington Discovery Institute at University Hospitals in Cleveland, Ohio invites Full Applications for the 2019 Harrington Scholar-Innovator Award, offering physician-scientists the resources to advance discoveries into medicines. Full Applications are accepted through May 10, 2018. Apply now at HarringtonDiscovery.org/Grant.
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Key Advances in Medicine eBook from Nature Reviews - FREE to download!   This essential resource summarizes the ground-breaking clinical and biomedical discoveries of 2017 and highlights the trends to watch out for in 2018, making it a must read eBook for anyone with an interest in medical science. Download for free
Comment: The evolving paradigm of cancer trials Shivaani Kummar p225 | doi:10.1038/nrd.2017.210 The development of anticancer therapies is evolving with the advent of novel targeted drugs. In this Comment, I summarize some of the key changes and discuss the various choices for the optimal development of a new generation of cancer therapeutics. Full Text | PDF
NEWS AND ANALYSIS		Top
Tissue-agnostic cancer drug pipeline grows, despite doubts Ken Garber p227 | doi:10.1038/nrd.2018.6 The FDA could soon approve the first drug developed explicitly for a tissue-agnostic cancer indication, but biological complexity may limit this approach. PDF
Vaccines take a shot at antimicrobial resistance Katie Kingwell p229 | doi:10.1038/nrd.2018.8 Economic and policy issues rein in industry enthusiasm for vaccines as an answer to drug-resistant bugs. PDF
BIOBUSINESS BRIEFS Market watch: Top drugs and companies by sales in 2017 Lisa Urquhart p232 | doi:10.1038/nrd.2018.42 PDF
Market watch: Upcoming market catalysts in Q2 2018 Alexandra Heller p233 | doi:10.1038/nrd.2018.43 PDF
AN AUDIENCE WITH George Yancopoulos p234 | doi:10.1038/nrd.2018.41 George Yancopoulos, CSO of Regeneron, discusses his 30 years at Regeneron, the company's evolving growth plans and the recent launch of a precompetitive collaboration to sequence 500,000 UK Biobank exomes. PDF
FROM THE ANALYST'S COUCH The atopic dermatitis market Eleni Pantazi, Gianluca Valenza, Manuela Hess & Bashar Hamad p237 | doi:10.1038/nrd.2017.192 The market for atopic dermatitis therapies is dominated by topical corticosteroids, but is poised to change with the recent approvals of dupilumab and crisaborole, as well as other drugs in clinical development. PDF
RESEARCH HIGHLIGHTS   Top Cancer: Tipping the splicing balance to kill cancer cells p239 | doi:10.1038/nrd.2018.38 PDF Antibacterial drugs: Discovering antibiotics through soil metagenomics p240 | doi:10.1038/nrd.2018.36 PDF Neurodevelopmental disorders: CRISPR to the rescue p240 | doi:10.1038/nrd.2018.39 PDF Asthma: Alternative route to airway relaxation p241 | doi:10.1038/nrd.2018.37 PDF Drug delivery: DNA nanorobots — seek and destroy p242 | doi:10.1038/nrd.2018.40 PDF   IN BRIEF Antivirals: Topical therapy for ocular herpes | Immunotherapy: iPSC-based cancer vaccine | Sepsis: Gut bacteria induce protective IgA | Infectious disease: Virus-based tuberculosis vaccine PDF Drug Discovery JOBS of the week Principal Scientist Drug Product Development Glenmark Pharmaceuticals Post-Doctoral Fellow Johns Hopkins University Postdoctoral Researcher University of Pennsylvania Assistant Professor University of Pittsburgh Department of Pediatrics Postdoctoral Scholar Oregon Health & Science University and Knight Cancer Institute More Science jobs from Drug Discovery EVENT Practical Aspects of Small-Molecule Drug Discovery 17.06.18 Hinxton, UK More science events from
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Animation on CRISPR: Gene editing and beyond The CRISPR-Cas9 system has revolutionised gene editing, but cutting DNA isn't all it can do. This Animation, from Nature Methods, explores where CRISPR might be headed next.  Watch the Animation >>  Produced with support from:  Dharmacon
REVIEWS		Top
Biased signalling: from simple switches to allosteric microprocessors Jeffrey S. Smith, Robert J. Lefkowitz & Sudarshan Rajagopal p243 | doi:10.1038/nrd.2017.229 A given G protein-coupled receptor can signal through a range of downstream transducers depending on the stimulating ligand, enabling biased signalling towards different biological outcomes. Lefkowitz and colleagues describe the latest advances in the field, including efforts to harness biased signalling for improved therapeutic outcomes. Abstract | Full Text | PDF
mRNA vaccines — a new era in vaccinology Norbert Pardi, Michael J. Hogan, Frederick W. Porter & Drew Weissman p261 | doi:10.1038/nrd.2017.243 mRNA vaccines represent a promising alternative to conventional vaccine approaches, but their application has been hampered by instability and delivery issues. Here, Pardi and colleagues discuss recent advances in mRNA vaccine technology, assess mRNA vaccines currently in development for cancer and infectious diseases and consider future directions and challenges. Abstract | Full Text | PDF
Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome Elizabeth M. Berry-Kravis, Lothar Lindemann, Aia E. Jønch, George Apostol, Mark F. Bear, Randall L. Carpenter, Jacqueline N. Crawley, Aurore Curie, Vincent Des Portes, Farah Hossain, Fabrizio Gasparini, Baltazar Gomez-Mancilla, David Hessl, Eva Loth, Sebastian H. Scharf, Paul P. Wang, Florian Von Raison, Randi Hagerman, Will Spooren & Sébastien Jacquemont p280 | doi:10.1038/nrd.2017.221 In this Review, a group of experts in fragile X syndrome analyses why the considerable drug development effort based on robust preclinical findings describing the mechanisms underlying this neurodevelopmental disorder has failed to translate into effective treatment and offers possible solutions to improve clinical trial design and therapeutic approaches. Abstract | Full Text | PDF
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CORRESPONDENCE		Top
Impact of target interactions on small-molecule drug disposition: an overlooked area Robert A. B. van Waterschoot, Neil J. Parrott, Andrés Olivares-Morales, Thierry Lavé, Malcolm Rowland & Dennis A. Smith p299 | doi:10.1038/nrd.2018.26 Full Text | PDF
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