Nature Reviews Drug Discovery contents December 2016 Volume 15 Number 12 pp 805-876

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Preventing or correcting cardiovascular disease in the future will require the discovery and validation of accurate and robust biomarkers, both for risk prognosis as well as treatment choice and monitoring.  Download for recently published manuscripts that provide the latest information on recent cardiovascular biomarker research and development.
TABLE OF CONTENTS
December 2016 Volume 15 Number 12		Advertisement
2015 2-year Impact Factor 47.120 Journal Metrics 2-year Median 31	In this issue Comment News and Analysis Research Highlights Reviews Also this month  Featured article: Epigenetic drug discovery: breaking through the immune barrier David F. Tough, Paul P. Tak, Alexander Tarakhovsky & Rab K. Prinjha	Tomorrow's medicines are on a different path to market than blockbuster drugs of the past, as pioneering scientists reimagine nearly every aspect of drug discovery R&D. They're refocusing their efforts on areas of strength, applying new skill sets, and establishing creatively-structured collaborations.  How can you apply these principles to the benefit of your own research?
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Poster on Molecular mechanisms of amyotrophic lateral sclerosis This poster from Nature Reviews Neuroscience provides an overview of the molecular and cellular mechanisms that have been proposed to contribute to the pathogenesis of amyotrophic lateral sclerosis, which is the most common form of motor neuron disease.  Download free online  Funded by a grant from MT Pharma America, Inc
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Have you read these highlight articles published in Experimental & Molecular Medicine? Mechanisms of aging-related proteinopathies in Caenorhabditis elegans Crucial role of HMGA1 in the self-renewal and drug resistance of ovarian cancer stem cells Read more open access contents.
Comment: Precision medicine and the changing role of regulatory agencies Alasdair Breckenridge, Hans-Georg Eichler & Jonathan P. Jarow p805 | doi:10.1038/nrd.2016.206 The growth of precision medicine presents challenges for the regulators of medicines, related to aspects that include the basis of evidence generation, patient involvement in the regulatory process, cost of new medicines and the need for new regulatory models. It also raises questions about the tolerance of risk, especially with early interventions for life-threatening diseases. Abstract | Full Text | PDF
NEWS AND ANALYSIS		Top
Cancer immunology community seeks better end points Elie Dolgin p807 | doi:10.1038/nrd.2016.254 Drug developers are still hunting for surrogate end points that can better capture the benefits of checkpoint inhibitors, oncolytic viruses and modified T cell therapies. PDF
Paring down the placebo response Asher Mullard p807 | doi:10.1038/nrd.2016.255 Pivotal trials of Alkermes's antidepressant ALKS 5461 show how a patented clinical trial design might be able to help control problematic placebo responses. PDF
NEWS IN BRIEF FDA approves antitoxin antibody Asher Mullard p811 | doi:10.1038/nrd.2016.257 PDF
NEWS IN BRIEF PCSK9 pipeline Asher Mullard p811 | doi:10.1038/nrd.2016.258 PDF
NEWS IN BRIEF EMA opens its data vaults Asher Mullard p811 | doi:10.1038/nrd.2016.259 PDF
NEWS IN BRIEF Access to medicines report cards Asher Mullard p811 | doi:10.1038/nrd.2016.260 PDF
BIOBUSINESS BRIEFS Market watch: Antibacterial innovation in European SMEs Ursula Theuretzbacher p812 | doi:10.1038/nrd.2016.229 PDF
BIOBUSINESS BRIEFS Regulatory watch: Challenges in drug development for central nervous system disorders: a European Medicines Agency perspective Florence Butlen-Ducuing, Frank Pétavy, Lorenzo Guizzaro, Malgorzata Zienowicz, Manuel Haas, Enrica Alteri, Tomas Salmonson & Emmanuelle Corruble p813 | doi:10.1038/nrd.2016.237 PDF
AN AUDIENCE WITH Carole Ho p816 | doi:10.1038/nrd.2016.251 Carole Ho, Chief Medical Officer at Denali Therapeutics, discusses how genetic findings have paved the way for one of the largest start-ups to take on neurodegeneration. PDF
FROM THE ANALYST'S COUCH Phase II and phase III failures: 2013-2015 Richard K. Harrison p817 | doi:10.1038/nrd.2016.184 This article analyses recent data on the reported causes of drug candidate attrition, which indicate that lack of efficacy is the reason for approximately half of all phase II and phase III failures. PDF
RESEARCH HIGHLIGHTS Top Biologics: Engineering T cells for customized therapeutic responses p819 | doi:10.1038/nrd.2016.249 PDF Anticancer drugs: Exploiting a weakness in colorectal cancers p820 | doi:10.1038/nrd.2016.247 PDF Anticancer drugs: Breaking up a pro-survival interaction p820 | doi:10.1038/nrd.2016.250 PDF Metabolic disorders: Hormone conjugate combats metabolic syndrome p821 | doi:10.1038/nrd.2016.243 PDF Immune disorders: Blocking the alternative complement pathway p822 | doi:10.1038/nrd.2016.235 PDF IN BRIEF Cancer: Blocking metastasis | Antibacterial agents: Microbiome-derived antibiotic identified | HIV: Achieving sustained remission | Drug design: Cannabinoid receptor structure revealed PDF Nature Reviews Drug Discovery JOBS of the week Drug Discovery Project Leader – Molecular and Cell Biology Beatson Institute for Cancer Research Assistant Professor: in "Functional Biochemistry, Cell Biology"and "Virology" at Kyoto University, "Synthetic organic chemistry, Chemistry for Drug Discovery" at Osaka University Kyoto University/Osaka University Scientist of Immunology Discovery Lab, Novartis Institutes for Biomedical Research Novartis Institutes for BioMedical Research Research Scientist, Computational Biology Celgene CITRE Senior Scientist - High Throughput Core Facility Merck & Co More Science jobs from
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REVIEWS		Top
Envelope-specific antibodies and antibody-derived molecules for treating and curing HIV infection Guido Ferrari, Barton F. Haynes, Scott Koenig, Jeffrey L. Nordstrom, David M. Margolis & Georgia D. Tomaras p823 | doi:10.1038/nrd.2016.173 Infection with HIV-1 is currently incurable as HIV-1 can persist as integrated provirus in the genome of latently infected CD4+ T cells, where it is invisible to the immune system and not responsive to drugs. Here, Ferrari and colleagues discuss the development of novel engineered bispecific and trispecific antibodies, particularly dual-affinity re-targeting (DART) proteins, designed to eradicate latently infected cells. Abstract | Full Text | PDF
Epigenetic drug discovery: breaking through the immune barrier David F. Tough, Paul P. Tak, Alexander Tarakhovsky & Rab K. Prinjha p835 | doi:10.1038/nrd.2016.185 The modification of epigenetic markers has become an attractive approach to cancer treatment. Here, Prinjha and colleagues discuss the use of epigenetic modulators in inflammatory diseases, which could be particularly amenable to this approach, as immune memory is often encoded in epigenetic changes. Although the field is still at an early stage, many compounds have been found to be more specific than previously thought and could soon enter clinical trials for autoimmune and inflammatory conditions. Abstract | Full Text | PDF
Calpain research for drug discovery: challenges and potential Yasuko Ono, Takaomi C. Saido & Hiroyuki Sorimachi p854 | doi:10.1038/nrd.2016.212 The calpain family of proteases are involved in numerous physiological and pathological processes. Here, Sorimachi and colleagues provide an overview of the calpain superfamily and calpain-related disorders, assess the various emerging approaches for therapeutically targeting calpains and highlight agents currently in clinical trials. Abstract | Full Text | PDF | Supplementary information
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