Nature Reviews Drug Discovery contents May 2017 Volume 16 Number 5 pp 297-367

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TABLE OF CONTENTS
May 2017 Volume 16 Number 5		Advertisement
2015 2-year Impact Factor 47.120 Journal Metrics 2-year Median 31	In this issue Comment News and Analysis Research Highlights Reviews Correction Also this month  Featured article: Strategies and challenges for the next generation of antibody–drug conjugates Alain Beck, Liliane Goetsch, Charles Dumontet & Nathalie Corvaïa	Genomics has met its match!  MAKE MORE MEANINGFUL CONNECTIONS A powerful first-line phenotypin g technology delivering a readout of the molecular phenotype and all its influences, both genetic and non-genetic. See how genomics and metabolomics are breaking through together.
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Comment: Accelerating development of scientific evidence for medical products within the existing US regulatory framework Rachel E. Sherman, Kathleen M. Davies, Melissa A. Robb, Nina L. Hunter & Robert M. Califf p297 | doi:10.1038/nrd.2017.25 Growing access to diverse 'real-world' data sources is enabling new approaches to close persistent evidence gaps about the optimal use of medical products in real-world practice. Here, we argue that contrary to widespread impressions, existing FDA regulations embody sufficient flexibility to accommodate the emerging tools and methods needed to achieve this goal. Abstract | Full Text | PDF | Supplementary information
NEWS AND ANALYSIS		Top
Nine paths to PCSK9 inhibition Asher Mullard p299 | doi:10.1038/nrd.2017.83 A lipid-modulating protein that exemplifies the value of human genetics for target validation has provided a fertile testing ground for new drug modalities including long-acting RNA interference drugs, vaccines against self-antigens, CRISPR therapeutics and small molecules that control ribosomal activity. PDF
CAR T therapies drive into new terrain Katie Kingwell p301 | doi:10.1038/nrd.2017.84 The FDA could soon approve the first chimeric antigen receptor (CAR) T therapies for blood cancers, but this young field is still working on how to address solid tumours, safety concerns and manufacturing issues. PDF
NEWS IN BRIEF FDA approves first drug for primary progressive multiple sclerosis Asher Mullard p305 | doi:10.1038/nrd.2017.88 PDF
FDA approves first deuterated drug Asher Mullard p305 | doi:10.1038/nrd.2017.89 PDF
FDA approves dupilumab for severe eczema Asher Mullard p305 | doi:10.1038/nrd.2017.90 PDF
BIOBUSINESS BRIEFS Regulatory watch: From big data to smart data: FDA's INFORMED initiative Sean Khozin, Geoffrey Kim & Richard Pazdur p306 | doi:10.1038/nrd.2017.26 PDF
BIOBUSINESS BRIEFS Trial watch: Trends in clinical trial design complexity Kenneth A. Getz & Rafael A. Campo p307 | doi:10.1038/nrd.2017.65 PDF
AN AUDIENCE WITH Thomas Lynch p308 | doi:10.1038/nrd.2017.69 Thomas Lynch, Bristol-Myers Squibb's new Chief Scientific Officer, discusses his R&D priorities, genomics diagnostics and the need for faster development of novel cancer drugs in earlier stages of disease. PDF
FROM THE ANALYST'S COUCH Trends in the market for antihypertensive drugs M. Adam Ali, Salman Rizvi & Basharut A. Syed p309 | doi:10.1038/nrd.2016.262 This analysis provides an overview of novel antihypertensive products, many of which are fixed-dose combinations of different drug classes, and provides an outlook on their likely impact on the market. PDF
RESEARCH HIGHLIGHTS Top Analgesia: Designing out opioid side effects p311 | doi:10.1038/nrd.2017.68 PDF Metabolic Disease: Protein tyrosine phosphatase inhibitor reverses diabetes p312 | doi:10.1038/nrd.2017.73 PDF Cancer: Belt and braces for BCR-ABL p312 | doi:10.1038/nrd.2017.79 PDF Anticancer therapy: Re-educating macrophages p313 | doi:10.1038/nrd.2017.82 PDF Regenerative medicine: Targeting adaptor protein interactions for nerve regrowth p314 | doi:10.1038/nrd.2017.85 PDF IN BRIEF Antibiotics: Reversing resistance | Viral infections: Targeting host kinases | Cancer: Identifying synergistic drug combinations | G protein-coupled receptors: Novel probe for MRGPRX2 PDF Drug Discovery JOBS of the week Head of Functional Characterization (m / f) Roche Diagnostics GmbH Program Director CART Cell Servier Sr. Scientific Researcher, NMR Spectroscopy - Structural Biology Genentech, Inc. Senior Scientist – Computational Medicinal Chemist Philip Morris International (PMI) Associate Director, Oncology In Vivo Pharmacology Janssen Pharmaceutica More Science jobs from Drug Discovery EVENT Microbiome Drug Development Summit 27.06.17 Boston, USA More science events from
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REVIEWS		Top
Strategies and challenges for the next generation of antibody-drug conjugates Alain Beck, Liliane Goetsch, Charles Dumontet & Nathalie Corvaia p315 | doi:10.1038/nrd.2016.268 Antibody-drug conjugate (ADCs), which aim to target highly cytotoxic drugs specifically to cancer cells, are one of the fastest growing classes of anticancer therapeutics, with more than 50 such agents currently in clinical trials. This Review discusses lessons learned and emerging strategies in the development of ADCs, including aspects such as target selection, the development of warheads, the optimization of linkers and new conjugation chemistries, and provides an overview of agents that are currently in clinical trials. Abstract | Full Text | PDF
Advances in islet encapsulation technologies Tejal Desai & Lonnie D. Shea p338 | doi:10.1038/nrd.2016.232 Islet transplantation can be an effective therapy for patients with type 1 diabetes, but its widespread use is limited by the need for lifelong immunosuppression. Here, Desai and Shea discuss the emerging potential of islet cell encapsulation including new strategies, assess key challenges facing the human translation of this technology and highlight encapsulation devices that have entered the clinic. Abstract | Full Text | PDF
Targeting phospholipase D in cancer, infection and neurodegenerative disorders H. Alex Brown, Paul G. Thomas & Craig W. Lindsley p351 | doi:10.1038/nrd.2016.252 Lipid second messengers such as phosphatidic acid (PtdOH) have a role in a wide range of pathological processes, and phospholipase D (PLD) enzymes are one of the major sources of signal-activated PtdOH generation. In this Review, Brown, Thomas and Lindsley discuss the development of PLD inhibitors, with a focus on isoform-specific inhibitors, and their potential applications in the treatment of cancer, neurodegeneration and infection. Abstract | Full Text | PDF
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Corrigendum: Bracing for the biosimilar wave Asher Mullard p367 | doi:10.1038/nrd.2017.64 Full Text | PDF
CORRECTION		Top
Advances in islet encapsulation technologies Tejal Desai & Lonnie D. Shea p367 | doi:10.1038/nrd.2017.67 Full Text | PDF
Erratum: An audience with Jay Bradner Asher Mullard p367 | doi:10.1038/nrd.2017.71 Full Text | PDF
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