Thursday, March 30, 2017

Nature Reviews Drug Discovery contents April 2017 Volume 16 Number 4 pp 223-296

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Nature Reviews Drug Discovery

Make target identification failure a thing of the past

40% of all clinical trial failures show no connection between a target and disease.  An additional 29% of clinical trials fail because the wrong target was selected.  What if you could take the pain out of target identification and make the process repeatable? See how you can by reaching beyond the data. 

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April 2017 Volume 16 Number 4Advertisement

Nature Reviews Drug Discovery cover
2015 2-year Impact Factor 47.120 Journal Metrics 2-year Median 31
In this issue
News and Analysis
Research Highlights

Also this month
 Featured article:
Marked for death: targeting epigenetic changes in cancer
Sophia Xiao Pfister & Alan Ashworth

Find out how Ginger got her voice back.
Behind every patient stands thousands of scientists and researchers working together to develop life-saving treatments. So what happens when a patient meets the people that helped save her life? Watch as Ginger Tam, a professional singer and lung cancer patient, meets the researchers who worked on her cancer treatment. 

View the video

Recommend to library
Harrington drug discovery research grants - awards up to $700,000
Harrington Discovery Institute at University Hospitals in Cleveland, Ohio solicits proposals for the 2018 Harrington Scholar-Innovator Award, offering physician-scientists the resources to advance discoveries into medicines. Letters of Intent accepted through April 5, 2017.
Apply now at 

BioPharma DealmakersCompany Profiles and Partnering Opportunities

Synthesis design tool that facilitates innovation

ICSYNTH from InfoChem, a Nature Research company, is a powerful computer-aided synthesis design software that can help you find the best route to synthesis. The advanced chemoinformatics algorithm can perform retrosynthetic analysis on target molecules and generate many possible synthetic routes, even if the target molecules are novel and/or unpublished.

Comment: Managing intellectual property to develop medicines for the world's poorest
Sylvie Fonteilles-Drabek, David Reddy & Timothy N. C. Wells
p223 | doi:10.1038/nrd.2017.24
It has been argued that patents impede the development and access of medicines for tropical diseases such as malaria. However, we believe that intellectual property can be a key tool to enable timely progression of drug development projects involving multiple partners and to ensure equitable access to successful products.
Abstract | Full Text | PDF


Fragment-based phenotypic screening is a hit
Monya Baker
p225 | doi:10.1038/nrd.2017.56
Libraries of functionalized small-molecule fragments that can be screened in whole cells could take phenotypic drug discovery to the next level, providing new opportunities against undertargeted proteins.

PRIME time at the EMA
Asher Mullard
p226 | doi:10.1038/nrd.2017.57
The European Medicines Agency's PRIME scheme to accelerate the development of promising drugs that address unmet medical needs has enrolled 19 products in its first year, showing considerable overlap with FDA breakthrough therapy designees but also key differences.

PARP inhibitors plough on
Asher Mullard
p229 | doi:10.1038/nrd.2017.61

FDA approves Novartis's CDK4/6 inhibitor
Asher Mullard
p229 | doi:10.1038/nrd.2017.62

TransCelerate makes progress
Asher Mullard
p229 | doi:10.1038/nrd.2017.63

Patent watch: Patent insight into polymer-free drug-eluting stents
Vadim Demidov, Daniel Currie & Justin Wen
p230 | doi:10.1038/nrd.2017.32

Market watch: Upcoming market catalysts in Q2 2017
Eric Ho
p231 | doi:10.1038/nrd.2017.47

Jay Bradner
p232 | doi:10.1038/nrd.2017.50
Jay Bradner, President of the Novartis Institutes for BioMedical Research, discusses increased interest in chemical biology and open science at Novartis.

The SCCHN drug market
Jennifer Bamford & Rachel M. Webster
p235 | doi:10.1038/nrd.2016.261
Two PD-1 directed checkpoint inhibitors have recently been approved for squamous cell carcinoma of the head and neck (SCCHN). Further checkpoint inhibitors, as well as other molecularly targeted agents and cytokine-based immunotherapies, are currently in the late-stage pipeline and are poised to change the treatment paradigm for SCCHN.



Infectious diseases: Targeting T cells to treat Chikungunya virus infections
p237 | doi:10.1038/nrd.2017.49

Hearing loss: Vector overcomes barrier to gene therapy delivery
p238 | doi:10.1038/nrd.2017.58

Liver disease: Conscious uncoupling in NASH
p238 | doi:10.1038/nrd.2017.60

Anticancer drugs: All roads lead to EZH2 inhibition
p239 | doi:10.1038/nrd.2017.55

Viral infections: Reinvigorating exhausted T cells in hepatitis B infection
p240 | doi:10.1038/nrd.2017.48


Ocular disorders: Vitamin B3 blocks glaucoma | Drug toxicity: Cardiac safety index for TKIs | Cardiovascular disease: Thioredoxin lowers hypertension | Cancer: Bacterium-based immunotherapy

Drug Discovery
JOBS of the week
Tobacco Cessation Counselor
Fred Hutchinson Cancer Research Center
Clinical Technologist I
Seattle Cancer Care Alliance
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Rowan University School of Osteopathic Medicine
Faculty Positions Available at School of Pharmaceutical Sciences, Tsinghua University
School of Pharmaceutical Sciences, Tsinghua University
Multiple Faculty Positions (Open Rank) for the Medical Discovery Team on Addiction
University of Minnesota
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RICT 2017 - 53rd International Conference on Medicinal Chemistry - Drug Discovery & Selection
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Animation: Alzheimer's disease 

Nature Neuroscience presents this animation, which introduces the molecular, cellular and physiological mechanisms associated with Alzheimer's disease and highlights some of the most recent advances in our understanding of the onset and progression of this devastating neurological condition.

Watch the Animation free online >>


Marked for death: targeting epigenetic changes in cancer
Sophia Xiao Pfister & Alan Ashworth
p241 | doi:10.1038/nrd.2016.256
Human cancers commonly have mutations in epigenetic regulatory genes, and several small molecules that target epigenetic regulators are in clinical trials. Here, Pfister and Ashworth discuss the biological complexity of epigenetic regulation in cancer and provide an overview of inhibitors that target gain-of-function mutations, as well as synthetic lethal approaches to target loss-of-function mutations in epigenetic regulators.
Abstract | Full Text | PDF

Dynamic versus static biomarkers in cancer immune checkpoint blockade: unravelling complexity
W. Joost Lesterhuis, Anthony Bosco, Michael J. Millward, Michael Small, Anna K. Nowak & Richard A. Lake
p264 | doi:10.1038/nrd.2016.233
Immune checkpoint blockade is a powerful anticancer approach; however, it only works for some patients. Here, Lesterhuis and colleagues argue that response to immune checkpoint blockade is a critical state transition of a complex system. They discuss recent advances in mathematics and network biology that might facilitate the identification of dynamic biomarkers, which in turn might help distinguish responders from non-responders and determine new targets for combination therapy.
Abstract | Full Text | PDF

From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors
Avi Ashkenazi, Wayne J. Fairbrother, Joel D. Leverson & Andrew J. Souers
p273 | doi:10.1038/nrd.2016.253
The B cell lymphoma 2 (BCL-2) family of proteins has a key role in regulating apoptosis and is often dysregulated in cancer. This has led to the development of several inhibitors of pro-survival BCL-2 family proteins such as BCL-2, BCL-XL and MCL1, including the BCL-2 inhibitor venetoclax, which has recently gained regulatory approval. Here, Ashkenazi and colleagues discuss the latest progress in developing small-molecule inhibitors of pro-survival BCL-2 family proteins.
Abstract | Full Text | PDF

Applications of chemogenomic library screening in drug discovery
Lyn H. Jones & Mark E. Bunnage
p285 | doi:10.1038/nrd.2016.244
Chemogenomic screening is increasingly being applied to expedite the conversion of phenotypic screening projects into target-based drug discovery approaches. Here, Jones and Bunnage discuss the principles of the creation and use of chemogenomic libraries, highlighting key examples and their applications, including target identification, drug repositioning and predictive toxicology.
Abstract | Full Text | PDF

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Correspondence: To cleave or not to cleave: therapeutic gene editing with and without programmable nucleases
Tod M. Woolf, Channabasavaiah B. Gurumurthy, Frederick Boyce & Eric B. Kmiec
p296 | doi:10.1038/nrd.2017.42
Full Text | PDF

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