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https://www.readbyqxmd.com/read/28545888/delivering-safer-immunotherapies-for-cancer
#1
Lauren Milling, Yuan Zhang, Darrell J Irvine
Cancer immunotherapy is now a powerful clinical reality, with a steady progression of new drug approvals and a massive pipeline of additional treatments in clinical and preclinical development. However, modulation of the immune system can be a double-edged sword: Drugs that activate immune effectors are prone to serious non-specific systemic inflammation and autoimmune side effects. Drug delivery technologies have an important role to play in harnessing the power of immune therapeutics while avoiding on-target/off-tumor toxicities...
May 22, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28545837/emerging-technologies-for-prediction-of-drug-candidate-efficacy-in-the-preclinical-pipeline
#2
Denis Menshykau
The pharmaceutical industry is tackling increasingly complex multifactorial diseases, resulting in increases in research & development (R&D) costs and reductions in the success rates for drug candidates during Phase 2 and 3 clinical trials, with a lack of efficacy being the primary reason for drug candidate failure. This implies that the predictive power of current preclinical assays for drug candidate efficacy is suboptimal and, therefore, that alternatives should be developed. Here, I review emerging in vitro, imaging, and in silico technologies and discuss their potential contribution to drug efficacy assessment...
May 22, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28544095/phenotypic-assays-for-mycobacterium-tuberculosis-infection
#3
Ok-Ryul Song, Nathalie Deboosere, Vincent Delorme, Christophe J Queval, Gaspard Deloison, Elisabeth Werkmeister, Frank Lafont, Alain Baulard, Raffaella Iantomasi, Priscille Brodin
Tuberculosis (TB) is still a major global threat, killing more than one million persons each year. With the constant increase of Mycobacterium tuberculosis strains resistant to first- and second-line drugs, there is an urgent need for the development of new drugs to control the propagation of TB. Although screenings of small molecules on axenic M. tuberculosis cultures were successful for the identification of novel putative anti-TB drugs, new drugs in the development pipeline remains scarce. Host-directed therapy may represent an alternative for drug development against TB...
May 19, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28538724/applying-systems-level-spectral-imaging-and-analysis-to-reveal-the-organelle-interactome
#4
Alex M Valm, Sarah Cohen, Wesley R Legant, Justin Melunis, Uri Hershberg, Eric Wait, Andrew R Cohen, Michael W Davidson, Eric Betzig, Jennifer Lippincott-Schwartz
The organization of the eukaryotic cell into discrete membrane-bound organelles allows for the separation of incompatible biochemical processes, but the activities of these organelles must be coordinated. For example, lipid metabolism is distributed between the endoplasmic reticulum for lipid synthesis, lipid droplets for storage and transport, mitochondria and peroxisomes for β-oxidation, and lysosomes for lipid hydrolysis and recycling. It is increasingly recognized that organelle contacts have a vital role in diverse cellular functions...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28532263/establishment-and-assessment-of-a-novel-in-vitro-bio-pk-pd-system-in-predicting-the-in-vivo-pharmacokinetics-and-pharmacodynamics-of-cyclophosphamide
#5
Shanshan Tong, Hong Sun, Caifu Xue, Hanmei Chen, Jing Liu, Huiying Yang, Ning Zhou, Xiaoqiang Xiang, Weimin Cai
1. A novel bio-pharmacokinetic/pharmacodynamic (PK/PD) system was established and assessed in predicting the PK parameters and PD effects of the model drug cyclophosphamide (CP) considering the interrelationships between drug metabolism, pharmacological effects and dynamic blood circulation processes in vitro. 2. The system contains a peristaltic pump, a reaction chamber with rat liver microsomes (RLMs) encapsulated in pluronic F127-acrylamide-bisacrylamide (FAB) hydrogels, an effector cell chamber and a recirculating pipeline...
May 23, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28530898/chronic-constipation-update-on-management
#6
REVIEW
Umar Hayat, Mohannad Dugum, Samita Garg
Managing chronic constipation involves identifying and treating secondary causes, instituting lifestyle changes, prescribing pharmacologic and nonpharmacologic therapies, and, occasionally, referring for surgery. Several new drugs have been approved, and others are in the pipeline.
May 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28527344/harnessing-plant-metabolic-diversity
#7
REVIEW
Charlie Owen, Nicola J Patron, Ancheng Huang, Anne Osbourn
Advances in DNA sequencing and synthesis technologies in the twenty-first century are now making it possible to build large-scale pipelines for engineering plant natural product pathways into heterologous production species using synthetic biology approaches. The ability to decode the chemical potential of plants by sequencing their transcriptomes and/or genomes and to then use this information as an instruction manual to make drugs and other high-value chemicals is opening up new routes to harness the vast chemical diversity of the Plant Kingdom...
May 17, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28527154/structure-based-classification-for-bile-salt-export-pump-bsep-inhibitors-using-comparative-structural-modeling-of-human-bsep
#8
Sankalp Jain, Melanie Grandits, Lars Richter, Gerhard F Ecker
The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline...
May 19, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28523014/harnessing-plant-biodiversity-for-the-discovery-of-novel-anticancer-drugs-targeting-microtubules
#9
REVIEW
Songbo Xie, Jun Zhou
The microtubule cytoskeleton plays a critical role in a wide range of cellular activities and has been shown to be a highly effective target for the treatment of human malignancies. Despite the recent focus on proteomics and high-throughput profiling, it is clear that analysis of plant extracts has yielded several highly efficacious microtubule-targeting agents (MTAs) currently in clinical use, as well as agents in the current pipeline with promising efficacy. To date, a large proportion of the world's plant biodiversity remains untapped by the pharmaceutical industry, presenting a major opportunity for the discovery of novel pharmacologically active lead compounds...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28520909/large-scale-data-driven-integrative-framework-for-extracting-essential-targets-and-processes-from-disease-associated-gene-data-sets
#10
Gaston K Mazandu, Emile R Chimusa, Kayleigh Rutherford, Elsa-Gayle Zekeng, Zoe Z Gebremariam, Maryam Y Onifade, Nicola J Mulder
Populations worldwide currently face several public health challenges, including growing prevalence of infections and the emergence of new pathogenic organisms. The cost and risk associated with drug development make the development of new drugs for several diseases, especially orphan or rare diseases, unappealing to the pharmaceutical industry. Proof of drug safety and efficacy is required before market approval, and rigorous testing makes the drug development process slow, expensive and frequently result in failure...
May 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28511997/thorough-qt-tqt-studies-concordance-with-torsadogenesis-and-an-evolving-cardiac-safety-testing-paradigm
#11
Barbara Wiśniowska, Zofia Tylutki, Sebastian Polak
Since 2005, when the International Conference on Harmonisation (ICH) E14 guideline was adopted, no drug has been withdrawn because of QTc prolongation or torsade de pointes arrhythmia. There are, however, costs associated with this success. In addition to the time and money invested, thorough QT (TQT) studies have limited the efficiency of the drug development pipeline. In this paper, we discuss the relevance of TQT trials as a tool for proarrhythmic risk prediction as a part of the debate regarding their usefulness...
May 13, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28503089/anticancer-chemodiversity-of-ranunculaceae-medicinal-plants-molecular-mechanisms-and-functions
#12
REVIEW
Da-Cheng Hao, Chun-Nian He, Jie Shen, Pei-Gen Xiao
The buttercup family, Ranunculaceae, comprising more than 2,200 species in at least 62 genera, mostly herbs, has long been used in folk medicine and worldwide ethnomedicine since the beginning of human civilization. Various medicinal phytometabolites have been found in Ranunculaceae plants, many of which, such as alkaloids, terpenoids, saponins, and polysaccharides, have shown anti-cancer activities in vitro and in vivo. Most concerns have been raised for two epiphany molecules, the monoterpene thymoquinone and the isoquinoline alkaloid berberine...
February 2017: Current Genomics
https://www.readbyqxmd.com/read/28501513/qsar-studies-of-the-bioactivity-of-hepatitis-c-virus-hcv-ns3-4a-protease-inhibitors-by-multiple-linear-regression-mlr-and-support-vector-machine-svm
#13
Zijian Qin, Maolin Wang, Aixia Yan
In this study, quantitative structure-activity relationship (QSAR) models using various descriptor sets and training/test set selection methods were explored to predict the bioactivity of hepatitis C virus (HCV) NS3/4A protease inhibitors by using a multiple linear regression (MLR) and a support vector machine (SVM) method. 512 HCV NS3/4A protease inhibitors and their IC50 values which were determined by the same FRET assay were collected from the reported literature to build a dataset. All the inhibitors were represented with selected nine global and 12 2D property-weighted autocorrelation descriptors calculated from the program CORINA Symphony...
May 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28499075/regulatory-considerations-on-endpoints-in-ovarian-cancer-drug-development
#14
REVIEW
Sanjeeve Balasubramaniam, Geoffrey S Kim, Amy E McKee, Richard Pazdur
Ovarian cancer remains a disease entity that is responsible for considerable morbidity and mortality among women worldwide. Modern drug research pipelines and accelerated drug development timelines applied to other disease entities have begun to make an impact on treatment options for patients with advanced ovarian cancer, as exemplified by the recent accelerated approval of 2 agents for this disease as the forerunners of a growing number of registrational trials. Regulatory flexibility for this serious and life-threatening condition spurs the consideration of intermediate endpoints for regulatory trial design, including potential applications in the development of newer therapeutic classes such as targeted therapies and immunotherapies for patients with advanced ovarian cancer...
May 12, 2017: Cancer
https://www.readbyqxmd.com/read/28498899/magenta-a-galaxy-implemented-tool-for-complete-tn-seq-analysis-and-data-visualization
#15
Katherine Maia McCoy, Margaret L Antonio, Tim van Opijnen
Motivation: Transposon insertion sequencing (Tn-Seq) is a microbial systems-level tool, that can determine on a genome-wide scale and in high-throughput, whether a gene, or a specific genomic region, is important for fitness under a specific experimental condition. Results: Here, we present MAGenTA, a suite of analysis tools which accurately calculate the growth rate for each disrupted gene in the genome to enable the discovery of: a) new leads for gene function, b) non coding RNAs; c) genes, pathways and ncRNAs that are involved in tolerating drugs or induce disease; d) higher order genome organization; and e) host-factors that affect bacterial host susceptibility...
May 11, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28496146/the-antifungal-pipeline-a-reality-check
#16
REVIEW
John R Perfect
Invasive fungal infections continue to appear in record numbers as the immunocompromised population of the world increases, owing partially to the increased number of individuals who are infected with HIV and partially to the successful treatment of serious underlying diseases. The effectiveness of current antifungal therapies - polyenes, flucytosine, azoles and echinocandins (as monotherapies or in combinations for prophylaxis, or as empiric, pre-emptive or specific therapies) - in the management of these infections has plateaued...
May 12, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28490260/emerging-treatments-for-alzheimer-s-disease-for-non-amyloid-and-non-tau-targets
#17
Ayesha Khan, Anne Corbett, Clive Ballard
The number of people with dementia, including Alzheimer's disease, is growing as a result of an ageing global population. Treatments available for AD only alleviate the symptoms of the disease, and are effective in some people with AD for a limited time. There is no disease-modifying treatment available, and despite research efforts, the underlying mechanisms of AD and optimal treatment targets have not been fully elucidated. Amyloid and tau are key pathological markers of AD with ongoing trials targeting both...
May 11, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28490214/emerging-amyloid-and-tau-targeting-treatments-for-alzheimer-s-disease
#18
Ayesha Khan, Anne Corbett, Clive Ballard
With an ageing global population, the number of people with dementia, and its main cause Alzheimer's disease (AD), is growing. current licensed treatments available for ad are only alleviate the symptoms of the disease, and are effective only in some people with ad for a limited time. there are currently no therapies that target the disease process. Areas covered: This review summarizes the available treatments for AD and the emerging therapies in the clinical trials pipeline. There are ongoing trials at various stages of development, targeting different mechanisms and pathways implicated in the disease...
May 19, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28486909/phenothiazine-a-better-scaffold-against-tuberculosis
#19
Satheeshkumar Sellamuthu, Mohammad Faizan Bhat, Ashok Kumar, Sushil Kumar Singh
New chemotherapeutic drugs are in dire need to improve tuberculosis (TB) control, since the situation is more baffling particularly due to the emergence of multidrug-resistant and extensively drug-resistant TB. Different chemical scaffolds are in drug discovery pipeline against tuberculosis. Among which, phenothiazines have shown significant in vitro activity against both susceptible and multidrug-resistant strains of M. tuberculosis. In addition, they enhance the activity of some agents employed for first-line treatment...
February 20, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28486449/drug-pipeline-1q17
#20
Laura DeFrancesco
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
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