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Nature Reviews. Drug Discovery

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https://www.readbyqxmd.com/read/28303026/strategies-and-challenges-for-the-next-generation-of-antibody-drug-conjugates
#1
REVIEW
Alain Beck, Liliane Goetsch, Charles Dumontet, Nathalie Corvaïa
Antibody-drug conjugates (ADCs) are one of the fastest growing classes of oncology therapeutics. After half a century of research, the approvals of brentuximab vedotin (in 2011) and trastuzumab emtansine (in 2013) have paved the way for ongoing clinical trials that are evaluating more than 60 further ADC candidates. The limited success of first-generation ADCs (developed in the early 2000s) informed strategies to bring second-generation ADCs to the market, which have higher levels of cytotoxic drug conjugation, lower levels of naked antibodies and more-stable linkers between the drug and the antibody...
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28303025/targeting-glutamate-signalling-in-depression-progress-and-prospects
#2
REVIEW
James W Murrough, Chadi G Abdallah, Sanjay J Mathew
Major depressive disorder (MDD) is severely disabling, and current treatments have limited efficacy. The glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine was recently repurposed as a rapidly acting antidepressant, catalysing the vigorous investigation of glutamate-signalling modulators as novel therapeutic agents for depressive disorders. In this Review, we discuss the progress made in the development of such modulators for the treatment of depression, and examine recent preclinical and translational studies that have investigated the mechanisms of action of glutamate-targeting antidepressants...
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28303024/lessons-from-immuno-oncology-a-new-era-for-cancer-nanomedicine
#3
Wen Jiang, Hengfeng Yuan, Charles K Chan, Christina A von Roemeling, Zuoqin Yan, Irving L Weissman, Betty Y S Kim
Despite a decade of intensive preclinical research, the translation of cancer nanomedicine to the clinic has been slow. Here, we discuss how recent lessons learned from the successes with immuno-oncology therapies could be applied to cancer nanomedicine and how this may help to overcome some of the key technical challenges in this field.
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28303023/market-watch-upcoming-market-catalysts-in-q2-2017
#4
Eric Ho
No abstract text is available yet for this article.
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28303022/to-cleave-or-not-to-cleave-therapeutic-gene-editing-with-and-without-programmable-nucleases
#5
Tod M Woolf, Channabasavaiah B Gurumurthy, Frederick Boyce, Eric B Kmiec
No abstract text is available yet for this article.
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28280262/marked-for-death-targeting-epigenetic-changes-in-cancer
#6
REVIEW
Sophia Xiao Pfister, Alan Ashworth
In the past few years, it has become clear that mutations in epigenetic regulatory genes are common in human cancers. Therapeutic strategies are now being developed to target cancers with mutations in these genes using specific chemical inhibitors. In addition, a complementary approach based on the concept of synthetic lethality, which allows exploitation of loss-of-function mutations in cancers that are not targetable by conventional methods, has gained traction. Both of these approaches are now being tested in several clinical trials...
March 10, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28280261/non-kinase-targets-of-protein-kinase-inhibitors
#7
REVIEW
Lenka Munoz
Kinome-wide profiling platforms have comprehensively identified the relevant kinases that are targeted by numerous protein kinase inhibitors. However, recent projects have begun to discover non-kinase targets of kinase inhibitors. These non-kinase targets can contribute to the desired or undesired activities of inhibitors, or act as silent bystanders. As a full awareness of a drug's mechanism of action is crucial for the interpretation of results and for successful preclinical and clinical drug development, these discoveries highlight the importance of understanding the pharmacology of kinase inhibitors beyond the kinome...
March 10, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28280260/trends-in-the-market-for-antihypertensive-drugs
#8
M Adam Ali, Salman Rizvi, Basharut A Syed
No abstract text is available yet for this article.
March 10, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28280259/patent-watch-patent-insight-into-polymer-free-drug-eluting-stents
#9
Vadim Demidov, Daniel Currie, Justin Wen
No abstract text is available yet for this article.
March 10, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28232726/accelerating-development-of-scientific-evidence-for-medical-products-within-the-existing-us-regulatory-framework
#10
Rachel E Sherman, Kathleen M Davies, Melissa A Robb, Nina L Hunter, Robert M Califf
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.
February 24, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28232725/managing-intellectual-property-to-develop-medicines-for-the-world-s-poorest
#11
Sylvie Fonteilles-Drabek, David Reddy, Timothy N C Wells
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.
February 24, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28232724/regulatory-watch-from-big-data-to-smart-data-fda-s-informed-initiative
#12
Sean Khozin, Geoffrey Kim, Richard Pazdur
No abstract text is available yet for this article.
February 24, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209992/from-basic-apoptosis-discoveries-to-advanced-selective-bcl-2-family-inhibitors
#13
REVIEW
Avi Ashkenazi, Wayne J Fairbrother, Joel D Leverson, Andrew J Souers
Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-XL dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209987/targeting-phospholipase-d-in-cancer-infection-and-neurodegenerative-disorders
#14
REVIEW
H Alex Brown, Paul G Thomas, Craig W Lindsley
Lipid second messengers have essential roles in cellular function and contribute to the molecular mechanisms that underlie inflammation, malignant transformation, invasiveness, neurodegenerative disorders, and infectious and other pathophysiological processes. The phospholipase D (PLD) isoenzymes PLD1 and PLD2 are one of the major sources of signal-activated phosphatidic acid (PtdOH) generation downstream of a variety of cell-surface receptors, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and integrins...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28154410/targeting-iron-metabolism-in-drug-discovery-and-delivery
#15
REVIEW
Bart J Crielaard, Twan Lammers, Stefano Rivella
Iron fulfils a central role in many essential biochemical processes in human physiology; thus, proper processing of iron is crucial. Although iron metabolism is subject to relatively strict physiological control, numerous disorders, such as cancer and neurodegenerative diseases, have recently been linked to deregulated iron homeostasis. Consequently, iron metabolism constitutes a promising and largely unexploited therapeutic target for the development of new pharmacological treatments for these diseases. Several iron metabolism-targeted therapies are already under clinical evaluation for haematological disorders, and these and newly developed therapeutic agents are likely to have substantial benefit in the clinical management of iron metabolism-associated diseases, for which few efficacious treatments are currently available...
February 3, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28104905/applications-of-chemogenomic-library-screening-in-drug-discovery
#16
REVIEW
Lyn H Jones, Mark E Bunnage
The allure of phenotypic screening, combined with the industry preference for target-based approaches, has prompted the development of innovative chemical biology technologies that facilitate the identification of new therapeutic targets for accelerated drug discovery. A chemogenomic library is a collection of selective small-molecule pharmacological agents, and a hit from such a set in a phenotypic screen suggests that the annotated target or targets of that pharmacological agent may be involved in perturbing the observable phenotype...
January 20, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28082745/the-scchn-drug-market
#17
Jennifer Bamford, Rachel M Webster
No abstract text is available yet for this article.
January 13, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28057932/dynamic-versus-static-biomarkers-in-cancer-immune-checkpoint-blockade-unravelling-complexity
#18
REVIEW
W Joost Lesterhuis, Anthony Bosco, Michael J Millward, Michael Small, Anna K Nowak, Richard A Lake
Recently, there has been a coordinated effort from academic institutions and the pharmaceutical industry to identify biomarkers that can predict responses to immune checkpoint blockade in cancer. Several biomarkers have been identified; however, none has reliably predicted response in a sufficiently rigorous manner for routine use. Here, we argue that the therapeutic response to immune checkpoint blockade is a critical state transition of a complex system. Such systems are highly sensitive to initial conditions, and critical transitions are notoriously difficult to predict far in advance...
January 6, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28248945/anticancer-agents-engineered-platelets-deliver-immunotherapy
#19
Sarah Crunkhorn
No abstract text is available yet for this article.
March 1, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28248944/atherosclerosis-haematopoietic-mutation-promotes-atherogenesis
#20
Sarah Crunkhorn
No abstract text is available yet for this article.
March 1, 2017: Nature Reviews. Drug Discovery
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