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


Discovery of a Tin-Piperonal-Entecavir Schiff Base Compound That Overcomes Multidrug Resistance by Inhibiting P-Glycoprotein.

Assay Drug Dev Technol 2018 May/Jun;16(4):205-211. Epub 2018 Jun 7.

4 Department of Chemistry, Hazara University , Mansehra, Pakistan .

The presence of P-glycoprotein in the human intestine represents a significant barrier to effective drug therapy. These proteins form a multidrug-resistant barrier to most drugs, especially those administered orally. Thus, strategies are needed to prepare molecules to combat these resistant proteins and enable an increase in drug efficacy. Read More

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Cholesterol Unbound RORγt Protein Enables a Sensitive Inverse Agonist Screening.

Assay Drug Dev Technol 2018 May/Jun;16(4):194-204. Epub 2018 Jun 6.

1 Biomolecular Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Fujisawa, Japan .

The retinoic acid-related orphan receptor gamma T (RORγt) plays an important role in Th17 cell proliferation and functionality. Thus, RORγt inverse agonists are thought to be potent therapeutic agents for Th17-mediated autoimmune diseases, such as rheumatoid arthritis, asthma, inflammatory bowel disease, and psoriasis. Although RORγt has constitutive activity, it is recognized that the receptor is physiologically regulated by various cholesterol derivatives. Read More

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June 2018
1 Read

Engineered EF-Tu and tRNA-Based FRET Screening Assay to Find Inhibitors of Protein Synthesis in Bacteria.

Assay Drug Dev Technol 2018 May/Jun;16(4):212-221. Epub 2018 Jun 5.

Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School , Newark, New Jersey.

Antibiotic-resistant infections that do not respond to available drugs are becoming more common. Methicillin-resistant Staphylococcus aureus, carbapenem-resistant enterobacteria ("superbugs"), and many others pose a continuous threat to public health. To provide tools to combat such deadly infections, we present in this study a homogeneous assay focused on an insufficiently addressed molecular interaction linked to ribosomal translation. Read More

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Changes on the Horizon for Drug Repurposing, Rescue, and Repositioning at ASSAY.

Assay Drug Dev Technol 2018 May/Jun;16(4):193. Epub 2018 Jun 5.

2 Editor, Drug Repurposing, Rescue, and Repositioning (DRRR) Advisory Board.

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Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Bradycardiac Effects Caused by Co-Administration of Sofosbuvir and Amiodarone.

Assay Drug Dev Technol 2018 May/Jun;16(4):222-229. Epub 2018 May 30.

1 Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University , Guangzhou, China .

Co-administration of sofosbuvir, an anti-hepatitis C virus medication, and antiarrhythmic amiodarone causes symptomatic severe bradycardia in patients and animal models. However, in a few in vitro studies, the combination of sofosbuvir and amiodarone resulted in tachycardiac effects in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This discrepancy may be attributable to the use of immature hiPSC-CMs in the in vitro studies. Read More

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May 2018
2 Reads

High-Throughput Gene Expression Profiles to Define Drug Similarity and Predict Compound Activity.

Assay Drug Dev Technol 2018 Apr;16(3):162-176

1 Janssen Research & Development , A Division of Janssen Pharmaceutica NV, Computational Sciences, Discovery Sciences, Beerse, Belgium .

By adding biological information, beyond the chemical properties and desired effect of a compound, uncharted compound areas and connections can be explored. In this study, we add transcriptional information for 31K compounds of Janssen's primary screening deck, using the HT L1000 platform and assess (a) the transcriptional connection score for generating compound similarities, (b) machine learning algorithms for generating target activity predictions, and (c) the scaffold hopping potential of the resulting hits. We demonstrate that the transcriptional connection score is best computed from the significant genes only and should be interpreted within its confidence interval for which we provide the stats. Read More

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April 2018
1 Read

A High-Throughput Time-Resolved Fluorescence Energy Transfer Assay to Screen for Modulators of RGS7/Gβ5/R7BP Complex.

Assay Drug Dev Technol 2018 Apr;16(3):150-161

1 Department of Neuroscience, The Scripps Research Institute , Jupiter, Florida.

G protein-coupled receptors (GPCRs) are excellent drug targets exploited by majority of the Food and Drug Administration-approved medications, but when modulated, are often accompanied by significant adverse effects. Targeting of other elements in GPCR pathways for improved safety and efficacy is thus an unmet need. The strength of GPCR signaling is tightly regulated by regulators of G protein signaling (RGS) proteins, making them attractive drug targets. Read More

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April 2018
1 Read

Effect of 2-Phenylethanol as Antifungal Agent and Common Antifungals (Amphotericin B, Fluconazole, and Itraconazole) on Candida Species Isolated from Chronic and Recurrent Cases of Candidal Vulvovaginitis.

Assay Drug Dev Technol 2018 Apr;16(3):141-149

2 Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences , Tehran, Iran .

The antifungal effects of 2-phenylethanol are clearly visible through its intervention in Candida morphogenesis. Chronic and recurrent vulvovaginitis, however, does not respond to this standard experimental therapy; therefore, the study presented in this article investigated the effect of common antifungal drugs (amphotericin B [AMB], fluconazole [FLU], and itraconazole [ITC]), in combination with 2-phenylethanol, on the Candida species isolated from cases of chronic and recurrent vulvovaginitis, thereby allowing the recommendation of a more appropriate treatment option. Forty isolates from patients with chronic and recurrent vaginal candidiasis were investigated in this experimental study. Read More

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April 2018
1 Read

Literature Search and Review.

Assay Drug Dev Technol 2018 Apr;16(3):133-140

2 Novartis Institutes for BioMedical Research , Cambridge, Massachusetts.

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April 2018
1 Read

Development of a Time-Resolved Fluorescence Resonance Energy Transfer Ultrahigh-Throughput Screening Assay for Targeting the NSD3 and MYC Interaction.

Assay Drug Dev Technol 2018 Feb/Mar;16(2):96-106

1 Department of Pharmacology, Emory University School of Medicine , Atlanta, Georgia .

Epigenetic modulators play critical roles in reprogramming of cellular functions, emerging as a new class of promising therapeutic targets. Nuclear receptor binding SET domain protein 3 (NSD3) is a member of the lysine methyltransferase family. Interestingly, the short isoform of NSD3 without the methyltransferase fragment, NSD3S, exhibits oncogenic activity in a wide range of cancers. Read More

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March 2019
2 Reads

Utility of Resazurin, Horseradish Peroxidase, and NMR Assays to Identify Redox-Related False-Positive Behavior in High-Throughput Screens.

Assay Drug Dev Technol 2018 Apr 2;16(3):171-191. Epub 2018 Apr 2.

1 Oncology IMED , AstraZeneca, Cambridge, United Kingdom .

Discerning false positives from true actives in high-throughput screening (HTS) output is fraught with difficulty as the reason of anomalous activity seen for compounds is often not clear-cut. In this study, we introduce a novel medium-throughput NMR assay for the identification of redox-cycling compounds (RCCs), which is based on detection of oxidation of a reducing agent. We compare its outcomes to those from horseradish peroxidase (HRP)/phenol red and resazurin (RZ)-based assays that are more commonly used for triaging HTS outputs. Read More

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April 2018
1 Read

Development of a Neo-Epitope Specific Assay for Serological Assessment of Type VII Collagen Turnover and Its Relevance in Fibroproliferative Disorders.

Assay Drug Dev Technol 2018 Feb/Mar;16(2):123-131. Epub 2018 Mar 1.

1 Biomarkers and Research , Nordic Bioscience, Herlev, Denmark .

Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients with systemic sclerosis (SSc), whereas reduced levels in the airways have been related to asthma. Read More

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March 2018
1 Read

Ebselen Reversibly Inhibits Human Glutamate Dehydrogenase at the Catalytic Site.

Assay Drug Dev Technol 2018 Feb/Mar;16(2):115-122. 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

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February 2018
2 Reads

Preparation of Vitamin E-Containing High-Density Lipoprotein and Its Protective Efficacy on Macrophages.

Assay Drug Dev Technol 2018 Feb/Mar;16(2):107-114. 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

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February 2018
1 Read

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

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February 2018
1 Read

Literature Search and Review.

Assay Drug Dev Technol 2018 Feb/Mar;16(2):65-73. Epub 2018 Feb 14.

2 Novartis Institutes for BioMedical Research , Cambridge, Massachusetts.

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February 2018
1 Read

Integration of Antibody Array Technology into Drug Discovery and Development.

Assay Drug Dev Technol 2018 Feb/Mar;16(2):74-95. 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

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February 2018
4 Reads

2017 Acknowledgment of Reviewers.

Authors:

Assay Drug Dev Technol 2018 Feb/Mar;16(2):132. Epub 2018 Feb 1.

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February 2018
1 Read

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

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January 2018
2 Reads

Research in Rare Disease: From Genomics to Proteomics.

Authors:
Jessica Lacoste

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

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January 2018
2 Reads

FLECS Technology for High-Throughput Single-Cell Force Biology and Screening.

Authors:
Ivan Pushkarsky

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

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January 2018
8 Reads

Old Compounds, New Uses, New Ways: Many Ways.

Authors:
Hermann Mucke

Assay Drug Dev Technol 2017 Dec;15(8):353

Editor, Drug Repurposing, Rescue, and Repositioning (DRRR) Advisory Board.

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December 2017
2 Reads

Drug Repurposing Patent Applications April-June 2017.

Assay Drug Dev Technol 2017 Dec;15(8):372-377

H.M. Pharma Consultancy , Wien, Austria .

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December 2017
2 Reads

Drug Repurposing Patent Applications July-September 2017.

Assay Drug Dev Technol 2017 Dec;15(8):378-382

H.M. Pharma Consultancy , Wien, Austria .

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December 2017
2 Reads

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

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January 2018
3 Reads

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

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December 2017
13 Reads

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

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December 2017
17 Reads

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

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January 2018
5 Reads

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

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June 2018
5 Reads

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

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June 2018
2 Reads

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

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June 2018
2 Reads

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

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December 2017
5 Reads
2.08 Impact Factor

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

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June 2018
3 Reads
2.08 Impact Factor

Literature Search and Review.

Assay Drug Dev Technol 2017 Oct/Nov;15(7):307-313. Epub 2017 Oct 26.

2 Novartis Institutes for BioMedical Research , Cambridge, Massachusetts.

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October 2017
2 Reads

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

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May 2018
5 Reads

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 Ca levels with calcium-sensitive dyes. Read More

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May 2018
12 Reads

Society of Biomolecular Imaging and Informatics Special Issue.

Assay Drug Dev Technol 2017 Aug/Sep;15(6):237-238

2 Peter MacCallum Cancer Centre , Melbourne, Australia .

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August 2017
10 Reads

Society of Biomolecular Imaging and Informatics 4th Annual Meeting September 13-15, 2017.

Authors:

Assay Drug Dev Technol 2017 Aug/Sep;15(6):297-306

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August 2017
7 Reads

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

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May 2018
3 Reads

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

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May 2018
10 Reads

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

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May 2018
2 Reads

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

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December 2017
3 Reads

Literature Search and Review.

Assay Drug Dev Technol 2017 Jul;15(5):190-197

2 Novartis Institutes for BioMedical Research , Cambridge, Massachusetts.

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July 2017
2 Reads

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)P by 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

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July 2017
8 Reads

In the July 2017 Issue of ASSAY….

Authors:
Bruce Melancon

Assay Drug Dev Technol 2017 Jul;15(5):189

Editor-in-Chief.

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July 2017
2 Reads

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

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July 2017
2 Reads

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

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July 2017
7 Reads

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

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March 2018
8 Reads
2.08 Impact Factor