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Nature Reviews Drug Discovery contents May 2018 Volume 17 Number 5 pp 301-377

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Nature Reviews Drug Discovery

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Dr Ben Cross from Horizon Discovery discusses how CRISPR Screening powers drug discovery 

Horizon Discovery has developed a suite of functional genomic screening technologies, including a CRISPR-Cas9 platform aiming to help its partners to identify, evaluate and validate targets; to understand drug mechanisms of action, and to facilitate studies involving patient stratification.

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TABLE OF CONTENTS

May 2018 Volume 17, Issue 5

Comment
News and Analysis
Research Highlights
Analysis
Reviews
Correspondence
Corrigenda
 
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Comment

 

Glimmers in illuminating the druggable genome    pp301 - 302
Griffin Rodgers, Christopher Austin, James Anderson, Aaron Pawlyk, Christine Colvis, Ronald Margolis & Jenna Baker
doi:10.1038/nrd.2017.252
Much biomedical research continues to focus on a small proportion of the human genome that has already been studied intensively. The Illuminating the Druggable Genome programme, initiated as a pilot project by the US National Institutes of Health Common Fund in 2014, is now being implemented to accelerate the investigation of subsets of understudied proteins that have potential therapeutic relevance.

News and Analysis

 

Microglia-targeted candidates push the Alzheimer drug envelope    pp303 - 305
Asher Mullard
doi:10.1038/nrd.2018.65
Denali Therapeutics is taking a swing at neuroinflammation with a first-in-man trial of a RIPK1 inhibitor, while the company and others search for ways to target microglial biology more precisely.

Industry embraces virtual trial platforms    pp305 - 306
Elie Dolgin
doi:10.1038/nrd.2018.66
Site-less trials promise to speed up drug development — but obstacles to in-home data collection abound.

News in Brief

IDO takes a blow    p307
Asher Mullard
doi:10.1038/nrd.2018.67

Novartis grows its gene therapy ambitions    p307
Asher Mullard
doi:10.1038/nrd.2018.68

Cashing in with off-the-shelf CAR Ts    p307
Asher Mullard
doi:10.1038/nrd.2018.69

Biobusiness Briefs

Regulatory watch: FDA new drug approvals in Q1 2018    p309
Lisa Urquhart
doi:10.1038/nrd.2018.61

An Audience With

Anja König    p310
doi:10.1038/nrd.2018.60
Anja König, Global Head of the Novartis Venture Fund, discusses the changing corporate venture capital landscape.

From the analyst's couch

The gastroesophageal cancer drug market    pp311 - 312
Paul Wilcock & Rachel M. Webster
doi:10.1038/nrd.2018.35
Immune checkpoint inhibitors are forecast to expand the market for gastroesophageal cancer drugs, which is particularly large in Asia.

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Research Highlights

 

Cancer immunotherapy: The perfect match    p313
M. Teresa Villanueva
doi:10.1038/nrd.2018.62

Anticancer drugs: Flipping the switch for selective GSK3 inhibition    p314
Katie Kingwell
doi:10.1038/nrd.2018.63

Metabolic disease: Liver enzyme inflames fat    p315
Sarah Crunkhorn
doi:10.1038/nrd.2018.59

In Brief

Neurodegeneration: New strategy for SBMA therapy    p316
Sarah Crunkhorn
doi:10.1038/nrd.2018.55

Type 2 diabetes: Targeting glutamine metabolism    p316
Sarah Crunkhorn
doi:10.1038/nrd.2018.56

Malaria: Clues to vaccine design    p316
Sarah Crunkhorn
doi:10.1038/nrd.2018.57

Cancer: Mopping up a molecule for breast cancer survival    p316
Megan Cully
doi:10.1038/nrd.2018.58

 
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Analysis

 

Unexplored therapeutic opportunities in the human genome    pp317 - 332
Tudor I. Oprea, Cristian G. Bologa, Søren Brunak, Allen Campbell, Gregory N. Gan, Anna Gaulton, Shawn M. Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L. Johnson, Anneli Karlson, Andrew R. Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Stephen L. Mathias, Michael T. McManus, Terrence F. Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P. Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L. Roth, Stephan C. Schürer, Anton Simeonov, Larry A. Sklar, Noel Southall, Susumu Tomita, Ilinca Tudose, Oleg Ursu, Dušica Vidović, Anna Waller, David Westergaard, Jeremy J. Yang & Gergely Zahoránszky-Köhalmi
doi:10.1038/nrd.2018.14
In 2014, the Illuminating the Druggable Genome programme was launched to promote the exploration of currently understudied but potentially druggable proteins. This article discusses how the systematic collection and processing of a wide array of biological and chemical data as part of this programme has enabled the development of evidence-based criteria for tracking the target development level of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. It also highlights the nature of the unexplored therapeutic opportunities for major protein families.

Reviews

 

Chemical probes and drug leads from advances in synthetic planning and methodology    pp333 - 352
Christopher J. Gerry & Stuart L. Schreiber
doi:10.1038/nrd.2018.53
Strategies such as diversity-oriented synthesis aim to explore novel areas of chemical space efficiently by populating small-molecule screening libraries with compounds containing structural features that are typically under-represented in commercially available screening collections. This article highlights how the design and synthesis of such libraries have been enabled by modern synthetic chemistry and illustrates the impact of the resultant chemical probes and drug leads in a wide range of diseases.

Kinase inhibitors: the road ahead    pp353 - 377
Fleur M. Ferguson & Nathanael S. Gray
doi:10.1038/nrd.2018.21
Existing kinase inhibitor drugs predominantly target receptor tyrosine kinases in cancer. Here, Gray and Ferguson review novel kinase targets in oncology, degenerative diseases, inflammatory disorders and infectious diseases. Advances in medicinal chemistry, selectivity profiling and computer-aided drug design, which are enabling the design of improved kinase inhibitors, are discussed.

Correspondence

 

Senotherapeutics for healthy ageing    p377
Laura J. Niedernhofer & Paul D. Robbins
doi:10.1038/nrd.2018.44

Corrigenda

 

Unexplored therapeutic opportunities in the human genome    p377
Tudor I. Oprea, Cristian G. Bologa, Søren Brunak, Allen Campbell, Gregory N. Gan, Anna Gaulton, Shawn M. Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L. Johnson, Anneli Karlson, Andrew R. Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Stephen L. Mathias, Michael T. McManus, Terrence F. Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P. Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L. Roth, Stephan C. Schürer, Anton Simeonov, Larry A. Sklar, Noel Southall, Susumu Tomita, Ilinca Tudose, Oleg Ursu, Dušica Vidović, Anna Waller, David Westergaard, Jeremy J. Yang & Gergely Zahoránszky-Köhalmi
doi:10.1038/nrd.2018.52

Accelerating the development of therapeutic strategies for drug-resistant tuberculosis    p377
Michael J. Vjecha, Simon Tiberi & Alimuddin Zumla
doi:10.1038/nrd.2018.64

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