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    844 results match your criteria Assay and drug development technologies[Journal]

    1 OF 17

    Ebselen Reversibly Inhibits Human Glutamate Dehydrogenase at the Catalytic Site.
    Assay Drug Dev Technol 2018 Feb 22. Epub 2018 Feb 22.
    College of Pharmaceutical Sciences, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology , Hangzhou, China .
    Human glutamate dehydrogenase (GDH) plays an important role in neurological diseases, tumor metabolism, and hyperinsulinism-hyperammonemia syndrome (HHS). However, there are very few inhibitors known for human GDH. Recently, Ebselen was reported to crosslink with Escherichia coli GDH at the active site cysteine residue (Cys321), but the sequence alignment showed that the corresponding residue is Ala329 in human GDH. Read More

    Preparation of Vitamin E-Containing High-Density Lipoprotein and Its Protective Efficacy on Macrophages.
    Assay Drug Dev Technol 2018 Feb 22. Epub 2018 Feb 22.
    1 Department of Obstetrics and Gynecology, The Second Clinical Hospital, Jilin University , Changchun, Republic of China .
    Atherosclerosis is a major cause for cardiovascular diseases. High-density lipoprotein (HDL) may reduce atherosclerosis through several different mechanisms. HDL is composed of lipids, cholesterol, cholesteryl esters, triglycerides, and phospholipids, mainly phosphatidylcholine plus specialized proteins called apolipoproteins (apos). Read More

    Anticancer Drugs as Antibiofilm Agents in Candida albicans: Potential Targets.
    Assay Drug Dev Technol 2018 Feb 15. Epub 2018 Feb 15.
    School of Life Sciences (DST-FIST and UGC-SAP Sponsored) SRTM University (NAAC Accredited with "A" grade) , Nanded, Maharashtra, India .
    The human pathogen Candida albicans can grow as a biofilm on host tissues and on the surfaces of different prosthetic devices in a patient's body. Various studies have reported that biofilms formed by C. albicans are resistant to most of the currently used antibiotics including the widely prescribed drug, fluconazole. Read More

    Integration of Antibody Array Technology into Drug Discovery and Development.
    Assay Drug Dev Technol 2018 Feb 2. Epub 2018 Feb 2.
    1 Raybiotech, Inc. , Guangzhou, China .
    Antibody arrays represent a high-throughput technique that enables the parallel detection of multiple proteins with minimal sample volume requirements. In recent years, antibody arrays have been widely used to identify new biomarkers for disease diagnosis or prognosis. Moreover, many academic research laboratories and commercial biotechnology companies are starting to apply antibody arrays in the field of drug discovery. Read More

    Machine Learning Enables Live Label-Free Phenotypic Screening in Three Dimensions.
    Assay Drug Dev Technol 2018 Jan;16(1):51-63
    1 Centre for Regenerative Medicine, University of Edinburgh , Edinburgh, United Kingdom .
    There is a large amount of information in brightfield images that was previously inaccessible by using traditional microscopy techniques. This information can now be exploited by using machine-learning approaches for both image segmentation and the classification of objects. We have combined these approaches with a label-free assay for growth and differentiation of leukemic colonies, to generate a novel platform for phenotypic drug discovery. Read More

    Research in Rare Disease: From Genomics to Proteomics.
    Assay Drug Dev Technol 2018 Jan;16(1):12-14
    Terrence Donnelly Centre for Cellular and Biomolecular Research , Toronto, Canada .
    Jessica Lacoste from the Donnelly Centre at the University of Toronto was awarded best poster at the annual Society of Biomolecular Imaging and Informatics meeting held in San Diego, September 2017. Her work focuses on characterizing the protein localization of variants involved in rare disease. The current works and future directions of research in rare disease are summarized in the following overview. Read More

    FLECS Technology for High-Throughput Single-Cell Force Biology and Screening.
    Assay Drug Dev Technol 2018 Jan 21;16(1):7-11. Epub 2017 Dec 21.
    Department of Bioengineering, UCLA , Los Angeles, California.
    Dr. Ivan Pushkarsky from the Department of Bioengineering at UCLA and Forcyte Biotechnologies, Inc. was awarded The President's Innovation Award at the Annual Society of Biomolecular Imaging and Informatics meeting held in San Diego, September 2017. Read More

    High-Content Screening Comparison of Cancer Drug Accumulation and Distribution in Two-Dimensional and Three-Dimensional Culture Models of Head and Neck Cancer.
    Assay Drug Dev Technol 2018 Jan 7;16(1):27-50. Epub 2017 Dec 7.
    1 Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh , Pittsburgh, Pennsylvania.
    High cancer drug development attrition rates have provoked considerable debate about whether the two-dimensional tumor growth inhibition high-throughput screening assays used in pre-clinical lead discovery adequately reflect solid tumor complexity. We used automated high-content screening image acquisition and analysis methods to compare fluorescent drug uptake, accumulation, and distribution in Cal33 and FaDu head and neck cancer (HNC) monolayer and multicellular tumor spheroid (MCTS) models. Ellipticine, idarubicin, daunorubicin, and doxorubicin were studied because of their fluorescent properties and broad anti-tumor activities. Read More

    When Enough Is Enough: Decision Criteria for Moving a Known Drug into Clinical Testing for a New Indication in the Absence of Preclinical Efficacy Data.
    Assay Drug Dev Technol 2017 Dec 1;15(8):354-361. Epub 2017 Dec 1.
    1 Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center , Nashville, Tennessee.
    Many animal models of disease are suboptimal in their representation of human diseases and lack of predictive power in the success of pivotal human trials. In the context of repurposing drugs with known human safety, it is sometimes appropriate to conduct the "last experiment first," that is, progressing directly to human investigations. However, there are not accepted criteria for when to proceed straight to humans to test a new indication. Read More

    A Homogeneous Cell-Based Halide-Sensitive Yellow Fluorescence Protein Assay to Identify Modulators of the Cystic Fibrosis Transmembrane Conductance Regulator Ion Channel.
    Assay Drug Dev Technol 2017 Dec 27;15(8):395-406. Epub 2017 Nov 27.
    1 Department of Molecular Medicine, The Scripps Research Institute Molecular Screening Center , Scripps Florida, Jupiter, Florida.
    Cystic fibrosis (CF), an inherited genetic disease, is caused by mutation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes an ion channel involved in hydration maintenance by anion homeostasis. Ninety percent of CF patients possess one or more copies of the F508del CFTR mutation. This mutation disrupts trafficking of the protein to the plasma membrane and diminishes function of mature CFTR. Read More

    A Functional Kinase Short Interfering Ribonucleic Acid Screen Using Protease-Activated Receptor 2-Dependent Opening of Transient Receptor Potential Vanilloid-4.
    Assay Drug Dev Technol 2018 Jan 17;16(1):15-26. Epub 2017 Nov 17.
    1 School of Health and Biomedical Sciences, RMIT University , Bundoora, Australia .
    Protease-activated receptor 2 (PAR) is a proinflammatory G-protein coupled receptor (GPCR) that is activated by inflammatory proteases, and its activation initiates signaling pathways that modulate the nonselective cation channel transient receptor potential vanilloid-4 (TRPV4). PAR-dependent opening of TRPV4 has been attributed to kinase activation, but the identity of the responsible enzymes is unknown. Deciphering the signaling pathways involved in the PAR-dependent opening of TRPV4 may yield new targets for pain treatment. Read More

    Utility of Adenosine Monophosphate Detection System for Monitoring the Activities of Diverse Enzyme Reactions.
    Assay Drug Dev Technol 2017 Oct/Nov;15(7):330-341
    1 Research and Development , Promega Corporation, Madison, Wisconsin.
    Adenosine monophosphate (AMP) is a key cellular metabolite regulating energy homeostasis and signal transduction. AMP is also a product of various enzymatic reactions, many of which are dysregulated during disease conditions. Thus, monitoring the activities of these enzymes is a primary goal for developing modulators for these enzymes. Read More

    Overproduction of Erythromycin by Ultraviolet Mutagenesis and Expression of ermE Gene in Saccharopolyspora erythraea.
    Assay Drug Dev Technol 2017 Oct/Nov;15(7):314-319
    2 Department of Human Bacterial Vaccines Production, Razi Vaccine and Serum Research Institute , Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran .
    Erythromycin is a macrolide antibiotic with broad-spectrum activity against gram-positive bacteria that stops protein synthesis by binding to 50s ribosomal subunit. Classical and recombinant strain improvement, such as application of ultraviolet (UV) mutagenesis and selection of overproduction mutant, is the most important and convenient method in enhancement of antibiotic production. In the present study, Saccharopolyspora erythraea was mutagenized using UV lights and selection by tylosin resistance mutant to improve yield of erythromycin. Read More

    Standard Curves Are Necessary to Determine Pharmacological Properties for Ligands in Functional Assays Using Competition Binding Technologies.
    Assay Drug Dev Technol 2017 Oct/Nov;15(7):320-329
    2 Arvinas, Inc. , New Haven, Connecticut.
    Homogeneous functional assays that utilize competition binding technology are widely used for determining pharmacological properties such as intrinsic activity and potency. One example is time-resolved fluorescence resonance energy transfer (TR-FRET) 3',5'-cyclic adenosine monophosphate (cAMP) assays, where labeled cAMP (tracer) and a labeled anti-cAMP antibody bind together to produce a TR-FRET signal when the two constituents are proximal to each other. This signal is disrupted when unlabeled and cellularly generated cAMP competes with the tracer cAMP for binding to the labeled antibody. Read More

    High-Throughput Screening Identifies 1,4,5-Substituted 1,2,3-Triazole Analogs as Potent and Specific Antagonists of Pregnane X Receptor.
    Assay Drug Dev Technol 2017 Dec 7;15(8):383-394. Epub 2017 Nov 7.
    Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital , Memphis, Tennessee.
    Human pregnane X receptor (hPXR) is a nuclear receptor that regulates the expression of phase I and phase II drug-metabolism enzymes, as well as that of drug transporters. hPXR is a "xenobiotics sensor" and can be activated by structurally diverse compounds. The activation of hPXR by its agonists increases the clearance of xenobiotics by increasing the expression of drug-metabolism enzymes and drug transporters, possibly leading to drug toxicity, drug resistance, and other adverse drug reactions. Read More

    Risk of Late-Onset Alzheimer's Disease by Plasma Cholesterol: Rational In Silico Drug Investigation of Pyrrole-Based HMG-CoA Reductase Inhibitors.
    Assay Drug Dev Technol 2017 Oct/Nov;15(7):342-351. Epub 2017 Oct 27.
    1 Department of Biotechnology, Panjab University , Chandigarh, India .
    Alzheimer's disease (AD), a worldwide renowned progressive neurodegenerative disorder, is the most common cause of dementia. There are several studies on the important role of cholesterol metabolism in AD pathogenesis, which indicated that the high concentrations of serum cholesterol increase the risk of AD. Biosynthesis of the plasma cholesterol and other isoprenoids is catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) through the conversion of HMG-CoA to mevalonic acid in mevalonate pathway. Read More

    Improving Comprehension Efficiency of High Content Screening Data Through Interactive Visualizations.
    Assay Drug Dev Technol 2017 Aug/Sep;15(6):247-256
    2 Department of Information and Computing Sciences, Utrecht University , Utrecht, Netherlands .
    In this study, an experiment is conducted to measure the performance in speed and accuracy of interactive visualizations. A platform for interactive data visualizations was implemented using Django, D3, and Angular. Using this platform, a questionnaire was designed to measure a difference in performance between interactive and noninteractive data visualizations. Read More

    Phenotypic Assays for Characterizing Compound Effects on Induced Pluripotent Stem Cell-Derived Cardiac Spheroids.
    Assay Drug Dev Technol 2017 Aug/Sep;15(6):280-296
    1 Molecular Devices, LLC , Sunnyvale, California.
    Development of more complex, biologically relevant, and predictive cell-based assays for compound screening is a major challenge in drug discovery. The focus of this study was to establish high-throughput compatible three-dimensional (3D) cardiotoxicity assays using human induced pluripotent stem cell-derived cardiomyocytes. Using both high-content imaging and fast kinetic fluorescence imaging, the impact of various compounds on the beating rates and patterns of cardiac spheroids was monitored by changes in intracellular Calevels with calcium-sensitive dyes. Read More

    How Phenotypic Screening Influenced Drug Discovery: Lessons from Five Years of Practice.
    Assay Drug Dev Technol 2017 Aug/Sep;15(6):239-246. Epub 2017 Aug 11.
    1 Novartis Institutes for BioMedical Research (NIBR) , Chemical Biology and Therapeutics (CBT), Basel, Switzerland .
    Since 2011, phenotypic screening has been a trend in the pharmaceutical industry as well as in academia. This renaissance was triggered by analyses that suggested that phenotypic screening is a superior strategy to discover first-in-class drugs. Despite these promises and considerable investments, pharmaceutical research organizations have encountered considerable challenges with the approach. Read More

    Exploiting Analysis of Heterogeneity to Increase the Information Content Extracted from Fluorescence Micrographs of Transgenic Zebrafish Embryos.
    Assay Drug Dev Technol 2017 Aug/Sep;15(6):257-266. Epub 2017 Aug 11.
    1 University of Pittsburgh Drug Discovery Institute , Pittsburgh, Pennsylvania.
    Zebrafish embryos are a near-ideal animal model for drug discovery because of their high genetic and physiological similarity to mammals, small size, high fecundity, and optical transparency. The latter properties make zebrafish at larval stages especially suited for high-content analysis and high throughput screening (HTS). However, inherent biological complexity and the inability to screen multiple specimens in a single well present a challenge for HTS because limiting replicates and high variability often prevent assays from reaching the stringent performance criteria demanded of large-scale screening assays. Read More

    High-Content Assay Multiplexing for Vascular Toxicity Screening in Induced Pluripotent Stem Cell-Derived Endothelial Cells and Human Umbilical Vein Endothelial Cells.
    Assay Drug Dev Technol 2017 Aug/Sep;15(6):267-279. Epub 2017 Aug 3.
    1 Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas.
    Endothelial cells (ECs) play a major role in blood vessel formation and function. While there is longstanding evidence for the potential of chemical exposures to adversely affect EC function and vascular development, the hazard potential of chemicals with respect to vascular effects is not routinely evaluated in safety assessments. Induced pluripotent stem cell (iPSC)-derived ECs promise to provide a physiologically relevant, organotypic culture model that is amenable for high-throughput (HT) EC toxicant screening and may represent a viable alternative to traditional in vitro models, including human umbilical vein endothelial cells (HUVECs). Read More

    High-Throughput Analysis Identifying Drugs That Regulate Apolipoprotein A-I Synthesis.
    Assay Drug Dev Technol 2017 Dec 25;15(8):362-371. Epub 2017 Jul 25.
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida College of Medicine-Jacksonville , Jacksonville, Florida.
    Apolipoprotein A-I (apo A-I) is the primary antiatherogenic protein in high-density lipoprotein (HDL). Despite the controversy as to the clinical effectiveness of raising HDL, the search is ongoing for safe and effective drugs that increase HDL and apo A-I levels. To identify novel compounds that can increase hepatic apo A-I production, two drug libraries were screened. Read More

    Development of Three Orthogonal Assays Suitable for the Identification and Qualification of PIKfyve Inhibitors.
    Assay Drug Dev Technol 2017 Jul;15(5):210-219
    1 Department of Small Molecule Discovery Research, Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, Connecticut.
    FYVE-type zinc finger-containing phosphoinositide kinase (PIKfyve) catalyzes the formation of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P) from phosphatidylinositol 3-phosphate (PI(3)P). PIKfyve has been implicated in multiple cellular processes, and its role in the regulation of toll-like receptor (TLR) pathways and the production of proinflammatory cytokines has sparked interest in developing small-molecule PIKfyve inhibitors as potential therapeutics to treat autoimmune and inflammatory diseases. We developed three orthogonal assays to identify and qualify small-molecule inhibitors of PIKfyve: (1) a purified component microfluidic enzyme assay that measures the conversion of fluorescently labeled PI(3)P to PI(3,5)Pby purified recombinant full-length human 6His-PIKfyve (rPIKfyve); (2) an intracellular protein stabilization assay using the kinase domain of PIKfyve expressed in HEK293 cells; and (3) a cell-based functional assay that measures the production of interleukin (IL)-12p70 in human peripheral blood mononuclear cells stimulated with TLR agonists lipopolysaccharide and R848. Read More

    Identification of Antipneumococcal Molecules Effective Against Different Streptococcus pneumoniae Serotypes Using a Resazurin-Based High-Throughput Screen.
    Assay Drug Dev Technol 2017 Jul;15(5):198-209
    1 Antibacterial Resistance Research Laboratory, Discovery Biology Department, Institut Pasteur Korea , Seongnam-si, Korea.
    Streptococcus pneumoniae is a major human pathogen, causing around 1.6 million deaths worldwide each year. By optimizing a resazurin-based assay to detect S. Read More

    Assay of Calcium Transients and Synapses in Rat Hippocampal Neurons by Kinetic Image Cytometry and High-Content Analysis: An In Vitro Model System for Postchemotherapy Cognitive Impairment.
    Assay Drug Dev Technol 2017 Jul;15(5):220-236
    1 Vala Sciences Inc. , San Diego, California.
    Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Read More

    Analytical Characterization of Methyl-β-Cyclodextrin for Pharmacological Activity to Reduce Lysosomal Cholesterol Accumulation in Niemann-Pick Disease Type C1 Cells.
    Assay Drug Dev Technol 2017 May/Jun;15(4):154-166
    1 National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, Maryland.
    Methyl-β-cyclodextrin (MβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease type C1 (NPC1) patient fibroblasts. However, the pharmacological activity of MβCD reported by different laboratories varies. To determine the potential causes of this variation, we analyzed the mass spectrum characteristics, pharmacological activity of three preparations of MβCDs, and the protein expression profiles of NPC1 patient fibroblasts after treatment with different sources of MβCDs. Read More

    A High-Throughput Screening Assay for NKCC1 Cotransporter Using Nonradioactive Rubidium Flux Technology.
    Assay Drug Dev Technol 2017 May/Jun;15(4):167-177
    1 Aurora Biomed Inc. , Vancouver, Canada .
    A high-throughput screening (HTS) assay was developed for cotransporter, NKCC1, which is a potential target for the treatment of diverse disorders. This nonradioactive rubidium flux assay coupled with ion channel reader series provides a working screen for this target expressed in human embryonic kidney (HEK) cell line. An eightfold window of detection was achieved with the optimized assay. Read More

    High-Throughput Phenotyping of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Neurons Using Electric Field Stimulation and High-Speed Fluorescence Imaging.
    Assay Drug Dev Technol 2017 May/Jun;15(4):178-188. Epub 2017 May 19.
    1 InvivoSciences, Inc. , Madison, Wisconsin.
    Electrophysiology of excitable cells, including muscle cells and neurons, has been measured by making direct contact with a single cell using a micropipette electrode. To increase the assay throughput, optical devices such as microscopes and microplate readers have been used to analyze electrophysiology of multiple cells. We have established a high-throughput (HTP) analysis of action potentials (APs) in highly enriched motor neurons and cardiomyocytes (CMs) that are differentiated from human induced pluripotent stem cells (iPSCs). Read More

    Investigation of Classical Organic and Ionic Liquid Cosolvents for Early-Stage Screening in Fragment-Based Inhibitor Design with Unrelated Bacterial and Human Dihydrofolate Reductases.
    Assay Drug Dev Technol 2017 May/Jun;15(4):141-153. Epub 2017 Apr 20.
    1 Département de Biochimie, Université de Montréal , Québec, Canada .
    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. Read More

    Validating the Predicted Effect of Astemizole and Ketoconazole Using a Drosophila Model of Parkinson's Disease.
    Assay Drug Dev Technol 2017 Apr;15(3):106-112
    Parkure Ltd. , Edinburgh, United Kingdom .
    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. Read More

    Accelerating Precision Drug Development and Drug Repurposing by Leveraging Human Genetics.
    Assay Drug Dev Technol 2017 Apr 5;15(3):113-119. Epub 2017 Apr 5.
    4 Department of Biomedical Informatics, Vanderbilt University School of Medicine , Nashville, Tennessee.
    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. Read More

    Using Chemoinformatics, Bioinformatics, and Bioassay to Predict and Explain the Antibacterial Activity of Nonantibiotic Food and Drug Administration Drugs.
    Assay Drug Dev Technol 2017 Apr 27;15(3):89-105. Epub 2017 Mar 27.
    1 Arab International University Faculty of Pharmacy , Daraa, Syrian Arab Republic.
    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. Read More

    DissolvIt: An In Vitro Method for Simulating the Dissolution and Absorption of Inhaled Dry Powder Drugs in the Lungs.
    Assay Drug Dev Technol 2017 Feb/Mar;15(2):77-88
    5 Astra Zeneca Ltd , Lund, Sweden .
    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. DissolvItwas 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. Read More

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