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Nature Reviews. Drug Discovery

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https://www.readbyqxmd.com/read/29147032/emptying-the-stores-lysosomal-diseases-and-therapeutic-strategies
#1
REVIEW
Frances M Platt
Lysosomal storage disorders (LSDs) - designated as 'orphan' diseases - are inborn errors of metabolism caused by defects in genes that encode proteins involved in various aspects of lysosomal homeostasis. For many years, LSDs were viewed as unattractive targets for the development of therapies owing to their low prevalence. However, the development and success of the first commercial biologic therapy for an LSD - enzyme replacement therapy for type 1 Gaucher disease - coupled with regulatory incentives rapidly catalysed commercial interest in therapeutically targeting LSDs...
November 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29147031/metabolic-disease-ectopic-olfactory-receptor-activation-reverses-obesity
#2
Sarah Crunkhorn
No abstract text is available yet for this article.
November 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29147030/eric-rubin
#3
(no author information available yet)
No abstract text is available yet for this article.
November 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29147029/sepsis-stalking-a-new-target
#4
Katie Kingwell
No abstract text is available yet for this article.
November 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29147028/cancer-bispecific-antibody-directs-t-cells-to-solid-tumours
#5
Megan Cully
No abstract text is available yet for this article.
November 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29104285/the-atopic-dermatitis-market
#6
Eleni Pantazi, Gianluca Valenza, Manuela Hess, Bashar Hamad
No abstract text is available yet for this article.
November 6, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29104284/jak-inhibition-as-a-therapeutic-strategy-for-immune-and-inflammatory-diseases
#7
REVIEW
Daniella M Schwartz, Yuka Kanno, Alejandro Villarino, Michael Ward, Massimo Gadina, John J O'Shea
The discovery of cytokines as key drivers of immune-mediated diseases has spurred efforts to target their associated signalling pathways. Janus kinases (JAKs) are essential signalling mediators downstream of many pro-inflammatory cytokines, and small-molecule inhibitors of JAKs (jakinibs) have gained traction as safe and efficacious options for the treatment of inflammation-driven pathologies such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. Building on the clinical success of first-generation jakinibs, second-generation compounds that claim to be more selective are currently undergoing development and proceeding to clinical trials...
November 6, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29075003/trends-in-gpcr-drug-discovery-new-agents-targets-and-indications
#8
REVIEW
Alexander S Hauser, Misty M Attwood, Mathias Rask-Andersen, Helgi B Schiöth, David E Gloriam
G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, mostly due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report an up-to-date analysis of all GPCR drugs and agents in clinical trials, which reveals current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs (~34% of all drugs approved by the US Food and Drug Administration (FDA)) act at 108 unique GPCRs. Approximately 321 agents are currently in clinical trials, of which ~20% target 66 potentially novel GPCR targets without an approved drug, and the number of biological drugs, allosteric modulators and biased agonists has increased...
October 27, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29075002/drug-discovery-effectiveness-from-the-standpoint-of-therapeutic-mechanisms-and-indications
#9
REVIEW
Hsin-Pei Shih, Xiaodan Zhang, Alex M Aronov
The productivity of the pharmaceutical industry has been widely discussed in recent years, particularly with regard to concerns that substantial expenditures on research and development have failed to translate into approved drugs. Various analyses of this productivity challenge have focused on aspects such as attrition rates at particular clinical phases or the physicochemical properties of drug candidates, but relatively little attention has been paid to how the industry has performed from the standpoint of the choice of therapeutic mechanisms and their intended indications...
October 27, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29056749/trial-watch-tracing-investment-in-drug-development-for-alzheimer-disease
#10
Alpha Tom Kodamullil, Firas Zekri, Meemansa Sood, Bastian Hengerer, Luc Canard, Duncan McHale, Martin Hofmann-Apitius
No abstract text is available yet for this article.
October 23, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29026211/legacy-data-sharing-to-improve-drug-safety-assessment-the-etox-project
#11
Ferran Sanz, François Pognan, Thomas Steger-Hartmann, Carlos Díaz, Montserrat Cases, Manuel Pastor, Philippe Marc, Joerg Wichard, Katharine Briggs, David K Watson, Thomas Kleinöder, Chihae Yang, Alexander Amberg, Maria Beaumont, Anthony J Brookes, Søren Brunak, Mark T D Cronin, Gerhard F Ecker, Sylvia Escher, Nigel Greene, Antonio Guzmán, Anne Hersey, Pascale Jacques, Lieve Lammens, Jordi Mestres, Wolfgang Muster, Helle Northeved, Marc Pinches, Javier Saiz, Nicolas Sajot, Alfonso Valencia, Johan van der Lei, Nico P E Vermeulen, Esther Vock, Gerhard Wolber, Ismael Zamora
The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through the Innovative Medicines Initiative to explore this possibility.
October 13, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28983100/market-watch-innovation-in-the-preclinical-antibiotic-pipeline
#12
Ursula Theuretzbacher, Miloje Savic, Christine Årdal, Kevin Outterson
No abstract text is available yet for this article.
October 6, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28983098/tau-based-therapies-in-neurodegeneration-opportunities-and-challenges
#13
REVIEW
Chuanzhou Li, Jürgen Götz
Aggregates of the microtubule-associated protein tau are a defining feature of several neurodegenerative diseases that are collectively known as tauopathies, and constitute one of the hallmark lesions of Alzheimer disease (AD). Given the lack of efficacy to date of amyloid-β-targeted therapies for AD, interest is growing in tau as a potential alternative target. Several drug candidates, which are now in clinical trials, aim to reduce tau levels or to prevent the aggregation or pathological post-translation modifications of this protein...
October 6, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28959953/biomarker-strategy-in-lung-cancer
#14
Mine Esencay, Andrew Watson, Kaushiki Mukherjee, Delphine Hanicq, Steven I Gubernick
No abstract text is available yet for this article.
September 29, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28959952/deubiquitylating-enzymes-and-drug-discovery-emerging-opportunities
#15
REVIEW
Jeanine A Harrigan, Xavier Jacq, Niall M Martin, Stephen P Jackson
More than a decade after a Nobel Prize was awarded for the discovery of the ubiquitin-proteasome system and clinical approval of proteasome and ubiquitin E3 ligase inhibitors, first-generation deubiquitylating enzyme (DUB) inhibitors are now approaching clinical trials. However, although our knowledge of the physiological and pathophysiological roles of DUBs has evolved tremendously, the clinical development of selective DUB inhibitors has been challenging. In this Review, we discuss these issues and highlight recent advances in our understanding of DUB enzymology and biology as well as technological improvements that have contributed to the current interest in DUBs as therapeutic targets in diseases ranging from oncology to neurodegeneration...
September 29, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28935918/host-directed-therapies-for-bacterial-and-viral-infections
#16
REVIEW
Stefan H E Kaufmann, Anca Dorhoi, Richard S Hotchkiss, Ralf Bartenschlager
Despite the recent increase in the development of antivirals and antibiotics, antimicrobial resistance and the lack of broad-spectrum virus-targeting drugs are still important issues and additional alternative approaches to treat infectious diseases are urgently needed. Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives. The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology...
September 22, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28935915/rna-based-therapeutics-increasing-efficacy
#17
Sarah Crunkhorn
No abstract text is available yet for this article.
September 22, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28935914/neurodegenerative-disease-dlk-zips-across-neurodegeneration
#18
M Teresa Villanueva
No abstract text is available yet for this article.
September 22, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28935913/katrine-bosley
#19
(no author information available yet)
No abstract text is available yet for this article.
September 22, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28935912/neurological-disorders-reversing-rett-syndrome
#20
Sarah Crunkhorn
No abstract text is available yet for this article.
September 22, 2017: Nature Reviews. Drug Discovery
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