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Assay and Drug Development Technologies

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https://www.readbyqxmd.com/read/28426233/investigation-of-classical-organic-and-ionic-liquid-cosolvents-for-early-stage-screening-in-fragment-based-inhibitor-design-with-unrelated-bacterial-and-human-dihydrofolate-reductases
#1
Jacynthe L Toulouse, Sarah M J Abraham, Natalia Kadnikova, Dominic Bastien, Vincent Gauchot, Andreea R Schmitzer, Joelle N Pelletier
Drug design by methods such as fragment screening requires effective solubilization of millimolar concentrations of small organic compounds while maintaining the properties of the biological target. We investigate four organic solvents and three 1-butyl-3-methylimidazolium (BMIm)-based ionic liquids (ILs) as cosolvents to establish conditions for screening two structurally unrelated dihydrofolate reductases (DHFRs) that are prime drug targets. Moderate concentrations (10%-15%) of cosolvents had little effect on inhibition of the microbial type II R67 DHFR and of human DHFR (hDHFR), while higher concentrations of organic cosolvents generally decreased activity of both DHFRs...
April 20, 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28418694/drug-repurposing-patent-applications-october-december-2016
#2
Hermann A M Mucke
No abstract text is available yet for this article.
April 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28418693/validating-the-predicted-effect-of-astemizole-and-ketoconazole-using-a-drosophila-model-of-parkinson-s-disease
#3
Katarzyna Styczyńska-Soczka, Luigi Zechini, Lysimachos Zografos
Parkinson's disease is a growing threat to an ever-ageing population. Despite progress in our understanding of the molecular and cellular mechanisms underlying the disease, all therapeutics currently available only act to improve symptoms and do not stop the disease process. It is therefore imperative that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson's. Drug repurposing has been recognized as being equally as promising as de novo drug discovery in the field of neurodegeneration and Parkinson's disease specifically...
April 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28418692/drug-repurposing-patent-applications-january-march-2017
#4
Hermann A M Mucke
No abstract text is available yet for this article.
April 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28379727/accelerating-precision-drug-development-and-drug-repurposing-by-leveraging-human-genetics
#5
Jill M Pulley, Jana K Shirey-Rice, Robert R Lavieri, Rebecca N Jerome, Nicole M Zaleski, David M Aronoff, Lisa Bastarache, Xinnan Niu, Kenneth J Holroyd, Dan M Roden, Eric P Skaar, Colleen M Niswender, Lawrence J Marnett, Craig W Lindsley, Leeland B Ekstrom, Alan R Bentley, Gordon R Bernard, Charles C Hong, Joshua C Denny
The potential impact of using human genetic data linked to longitudinal electronic medical records on drug development is extraordinary; however, the practical application of these data necessitates some organizational innovations. Vanderbilt has created resources such as an easily queried database of >2.6 million de-identified electronic health records linked to BioVU, which is a DNA biobank with more than 230,000 unique samples. To ensure these data are used to maximally benefit and accelerate both de novo drug discovery and drug repurposing efforts, we created the Accelerating Drug Development and Repurposing Incubator, a multidisciplinary think tank of experts in various therapeutic areas within both basic and clinical science as well as experts in legal, business, and other operational domains...
April 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28346800/using-chemoinformatics-bioinformatics-and-bioassay-to-predict-and-explain-the-antibacterial-activity-of-nonantibiotic-food-and-drug-administration-drugs
#6
Nour Aldin Kahlous, Muhammad Al Mohdi Bawarish, Muhammad Arabi Sarhan, Manfred Küpper, Ali Hasaba, Mazen Rajab
Discovering of new and effective antibiotics is a major issue facing scientists today. Luckily, the development of computer science offers new methods to overcome this issue. In this study, a set of computer software was used to predict the antibacterial activity of nonantibiotic Food and Drug Administration (FDA)-approved drugs, and to explain their action by possible binding to well-known bacterial protein targets, along with testing their antibacterial activity against Gram-positive and Gram-negative bacteria...
April 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28322599/dissolvit-an-in-vitro-method-for-simulating-the-dissolution-and-absorption-of-inhaled-dry-powder-drugs-in-the-lungs
#7
Per Gerde, Maria Malmlöf, Lina Havsborn, Carl-Olof Sjöberg, Pär Ewing, Stefan Eirefelt, Katarina Ekelund
The main purpose of this work was to develop an in vitro method for simulating the dissolution and absorption of inhaled dry powder drugs that also mimics systemic pharmacokinetic data. A second purpose was to evaluate this method. DissolvIt(®) was developed as a simulation of the air-blood barrier of the upper airways, constituting: "airborne" particles deposited on a glass cover slip, a mucus simulant, a polycarbonate (basal) membrane, and a pumped albumin buffer simulating the pulmonary blood flow. The PreciseInhale(®) exposure system was used to aerosolize and deposit test formulations onto cover slips...
February 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28322598/screening-and-functional-profiling-of-small-molecule-hiv-1-entry-and-fusion-inhibitors
#8
Charline Giroud, Yuhong Du, Mariana Marin, Qui Min, Nathan T Jui, Haian Fu, Gregory B Melikyan
HIV-1 entry and fusion with target cells is an important target for antiviral therapy. However, a few currently approved treatments are not effective as monotherapy due to the emergence of drug resistance. This consideration has fueled efforts to develop new bioavailable inhibitors targeting different steps of the HIV-1 entry process. Here, a high-throughput screen was performed of a large library of 100,000 small molecules for HIV-1 entry/fusion inhibitors, using a direct virus-cell fusion assay in a 384 half-well format...
February 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27996302/determination-of-interference-during-in-vitro-pyrogen-detection-development-and-characterization-of-a-cell-based-assay
#9
Linda Palma, Francesca Rossetti, Sabrina Dominici, Costantina Buondelmonte, Marco B L Rocchi, Gian P Rizzardi, Giuliana Vallanti, Mauro Magnani
Contamination of pharmaceutical products and medical devices with pyrogens such as endotoxins is the most common cause of systemic inflammation and, in worst cases, of septic shock. Thus, quantification of pyrogens is crucial. The limulus amebocyte lysate (LAL)-based assays are the reference tests for in vitro endotoxin detection, in association with the in vivo rabbit pyrogen test (RPT), according to European Pharmacopoeia (EP 2.6.14), and U.S. Pharmacopoeia (USP <85>). However, several substances interfere with LAL assay, while RPT is not accurate, not quantitative, and raises ethical limits...
February 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28092461/sbi-2-hcs-hca-3d-imaging-best-practices-and-unmet-needs-colloquium
#10
Ann F Hoffman, Kaylene J Simpson, Peter Horvath, Carrie Lovitt, Serena Silver, Evan Easton, Daniel V LaBarbera, Melissa Mendez, Mark E Rothenberg, Jan Seldin, Judi Wardwell-Swanson, Myles Fennell
No abstract text is available yet for this article.
January 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28092460/a-three-dimensional-lymphatic-endothelial-cell-tube-formation-assay-to-identify-novel-kinases-involved-in-lymphatic-vessel-remodeling
#11
T Jessica Gambino, Steven P Williams, Carol Caesar, Daniel Resnick, Cameron J Nowell, Rae H Farnsworth, Marc G Achen, Steven A Stacker, Tara Karnezis
The lymphatic system is a series of vessels that transport cells and excess fluid from tissues to the blood vascular system. Normally quiescent, the lymphatics can grow or remodel in response to developmental, immunological, or cells pathological stimuli. Lymphatic vessels comprise lymphatic endothelial cells (LECs) that can respond to external growth factors by undergoing proliferation, migration, adhesion, and tube and lumen formation into new vessel structures, a process known as lymphangiogenesis. To understand the key gene and signaling pathways necessary for lymphangiogenesis and lymphatic vessel remodeling, we have developed a three-dimensional LEC tube formation assay to explore the role of kinase signaling in these processes...
January 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28092459/toward-high-throughput-and-multiplexed-imaging-of-genome-organization
#12
Eric F Joyce
Dr. Eric Joyce from the Department of Genetics at the University of Pennsylvania was awarded The President's Innovation award at the annual Society of Biomolecular Imaging and Informatics meeting held in Boston, September 2016. Chromosome interactions are a fundamental aspect of nuclear organization that can activate and silence genes or even direct chromosome rearrangements. However, the molecular mechanisms underlying how chromosomal segments find each other and form stable interactions within cells remain unknown...
January 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28005393/multiplexed-single-cell-imaging-past-present-and-future
#13
Jia-Ren Lin
Jia-Ren Lin from the Laboratory of Systems Pharmacology at Harvard Medical School was awarded best poster at the annual Society of Biomolecular Imaging and Informatics meeting held in Boston, September 2016. His work focuses on single-cell imaging, especially on developing new methods for simultaneously detecting many antigens, named cyclic immunofluorescence (CycIF). This method could be applied in different stages of drug development, from discovery phase, preclinical research to clinical research. The current works and future directions of CycIF method are summarized in the following overview...
January 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27788017/effect-size-measures-as-descriptors-of-assay-quality-in-high-content-screening-a-brief-review-of-some-available-methodologies
#14
Bartek Rajwa
The field of high-content screening (HCS) typically uses measures of screen quality conceived for fairly straightforward high-throughput screening (HTS) scenarios. However, in contrast to HTS, image-based HCS systems rely on multidimensional readouts reporting biological responses associated with complex cellular phenotypes. Not only is the dimensionality in which the screens operate higher, but also the scale of the individual features describing the quantified phenotypic changes is often smaller than what is seen in one-dimensional HTS platforms...
January 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27982706/drug-repurposing-patent-applications-april-june-2016
#15
Hermann A M Mucke
No abstract text is available yet for this article.
December 2016: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27982705/drug-repurposing-patent-applications-july-september-2016
#16
Hermann A M Mucke
No abstract text is available yet for this article.
December 2016: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27982704/tramadol-an-opioid-receptor-agonist-an-inhibitor-of-growth-morphogenesis-and-biofilm-formation-in-the-human-pathogen-candida-albicans
#17
Gunderao Hanumantrao Kathwate, S Mohan Karuppayil
Tramadol is a synthetic, centrally acting low-affinity agonist of μ-opioid receptors in humans. It is used as an analgesic and is shown to have local anesthetic action. In this study, we have tried to explore its anti-Candida potential. Minimum inhibitory concentration (MIC50) and minimum fungicidal concentration (MFC) values were established. MIC50 ranged from 2 to 4 mg/mL, whereas MFC was recorded at 8 mg/mL. Also, the effect of tramadol on germ tube formation, adhesion, and biofilms in Candida albicans was studied...
December 2016: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27982703/revisiting-repurposing
#18
Elizabeth R Sharlow
Drug repurposing can be a cost-effective strategy to identify new small molecule-based therapies. Thus, drug repurposing significantly influences the discovery of therapeutics, particularly for rare and neglected diseases, which are often constrained by limited research and development funds. The push for translational science and access to drug discovery-associated resources such as high throughput screening instrumentation, assay development expertise, and Food and Drug Administration-approved drug libraries have intensified interest in drug repurposing...
December 2016: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27922743/interview-with-farid-khan-phd
#19
(no author information available yet)
No abstract text is available yet for this article.
December 2016: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27631620/big-data-mining-and-adverse-event-pattern-analysis-in-clinical-drug-trials
#20
Callie Federer, Minjae Yoo, Aik Choon Tan
Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov ( https://clinicaltrials.gov/ ), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning...
December 2016: Assay and Drug Development Technologies
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