10 results match your criteria 1536-well yielded

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Synthetic fluorescent MYC probe: Inhibitor binding site elucidation and development of a high-throughput screening assay.

Bioorg Med Chem 2021 Jul 6;42:116246. Epub 2021 Jun 6.

Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, United States. Electronic address:

We report the discovery of a fluorescent small molecule probe. This probe exhibits an emission increase in the presence of the oncoprotein MYC that can be attenuated by a competing inhibitor. Hydrogen-deuterium exchange mass spectrometry analysis, rationalized by induced-fit docking, suggests it binds to the "coiled-coil" region of the leucine zipper domain. Read More

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Identification of Compounds That Promote Readthrough of Premature Termination Codons in the CFTR.

SLAS Discov 2021 Feb 5;26(2):205-215. Epub 2020 Oct 5.

Department of Molecular Medicine, Scripps Florida, The Scripps Research Institute Molecular Screening Center, Jupiter, FL, USA.

Cystic fibrosis (CF) is caused by a mutation of the Cystic Fibrosis Transmembrane Conductance Regulator () gene, which disrupts an ion channel involved in hydration maintenance via anion homeostasis. Nearly 5% of CF patients possess one or more copies of the allele, which results in a stop codon at residue 542, preventing full-length CFTR protein synthesis. Identifying small-molecule modulators of mutant CFTR biosynthesis that affect the readthrough of this and other premature termination codons to synthesize a fully functional CFTR protein represents a novel target area of drug discovery. Read More

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February 2021

A Cytotoxic Three-Dimensional-Spheroid, High-Throughput Assay Using Patient-Derived Glioma Stem Cells.

SLAS Discov 2018 09 11;23(8):842-849. Epub 2018 May 11.

1 Department of Molecular Medicine, Scripps Florida, Jupiter, FL, USA.

Glioblastoma (GBM) is the most aggressive primary brain cancer with an average survival time after diagnosis of only 12-14 months, with few (<5%) long-term survivors. A growing body of work suggests that GBMs contain a small population of glioma stem cells (GSCs) that are thought to be major contributors to treatment resistance and disease relapse. Identifying compounds that modulate GSC proliferation would provide highly valuable molecular probes of GSC-directed signaling. Read More

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September 2018

Drug Library Screening for the Identification of Ionophores That Correct the Mistrafficking Disorder Associated with Oxalosis Kidney Disease.

SLAS Discov 2017 08 31;22(7):887-896. Epub 2017 Jan 31.

1 Department of Molecular Therapeutics, Scripps Research Institute Molecular Screening Center, Scripps Research Institute, Jupiter, FL, USA.

Primary hyperoxaluria is the underlying cause of oxalosis and is a life-threatening autosomal recessive disease, for which treatment may require dialysis or dual liver-kidney transplantation. The most common primary hyperoxaluria type 1 (PH1) is caused by genetic mutations of a liver-specific enzyme alanine:glyoxylate aminotransferase (AGT), which results in the misrouting of AGT from the peroxisomes to the mitochondria. Pharmacoperones are small molecules with the ability to modify misfolded proteins and route them correctly within the cells, which may present an effective strategy to treat AGT misrouting in PH1 disorders. Read More

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Application of Parallel Multiparametric Cell-Based FLIPR Detection Assays for the Identification of Modulators of the Muscarinic Acetylcholine Receptor 4 (M4).

J Biomol Screen 2015 Aug 15;20(7):858-68. Epub 2015 Apr 15.

The Scripps Research Institute Molecular Screening Center, Scripps Florida, Jupiter, FL, USA Amgen Inc., Thousand Oaks, CA, USA.

Muscarinic acetylcholine receptors (mAChRs) have long been viewed as viable targets for novel therapeutic agents for the treatment of Alzheimer's disease and other disorders involving impaired cognitive function. In an attempt to identify orthosteric and allosteric modulators of the muscarinic acetylcholine receptor M(4) (M(4)), we developed a homogenous, multiparametric, 1536-well assay to measure M(4) receptor agonism, positive allosteric modulation (PAM), and antagonism in a single well. This assay yielded a Z' of 0. Read More

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Identification of Potent and Selective Inhibitors of the Plasmodium falciparum M18 Aspartyl Aminopeptidase (PfM18AAP) of Human Malaria via High-Throughput Screening.

J Biomol Screen 2014 Aug 11;19(7):1107-15. Epub 2014 Mar 11.

The Scripps Research Institute Molecular Screening Center, Scripps Florida, Jupiter, FL, USA

The target of this study, the PfM18 aspartyl aminopeptidase (PfM18AAP), is the only AAP present in the genome of the malaria parasite Plasmodium falciparum. PfM18AAP is a metallo-exopeptidase that exclusively cleaves N-terminal acidic amino acids glutamate and aspartate. It is expressed in parasite cytoplasm and may function in concert with other aminopeptidases in protein degradation, of, for example, hemoglobin. Read More

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A homogenous luminescence assay reveals novel inhibitors for giardia lamblia carbamate kinase.

Curr Chem Genomics 2012 31;6:93-102. Epub 2012 Dec 31.

National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

The human pathogen Giardia lamblia is an anaerobic protozoan parasite that causes giardiasis, one of the most common diarrheal diseases worldwide. Although several drugs are available for the treatment of giardisis, resistance to these drugs has been reported and is likely to increase. The Giardia carbamate kinase (glCK) plays an essential role in Giardia metabolism and has no homologs in humans, making it an attractive candidate for anti-Giardia drug development. Read More

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February 2013

A miniaturized glucocorticoid receptor translocation assay using enzymatic fragment complementation evaluated with qHTS.

Comb Chem High Throughput Screen 2008 Aug;11(7):545-59

National Institutes of Health, National Human Genome Research Institute, NIH Chemical Genomics Center, Bethesda, MD 20892-3370, USA.

Nuclear translocation is an important step in glucocorticoid receptor (GR) signaling and assays that measure this process allow the identification of nuclear receptor ligands independent of subsequent functional effects. To facilitate the identification of GR-translocation agonists, an enzyme fragment complementation (EFC) cell-based assay was scaled to a 1536-well plate format to evaluate 9,920 compounds using a quantitative high throughput screening (qHTS) strategy where compounds are assayed at multiple concentrations. In contrast to conventional assays of nuclear translocation the qHTS assay described here was enabled on a standard luminescence microplate reader precluding the requirement for imaging methods. Read More

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Characterization of the 5-HT2b receptor in evaluation of aequorin detection of calcium mobilization for miniaturized GPCR high-throughput screening.

J Biomol Screen 2008 Jul 19;13(6):486-93. Epub 2008 Jun 19.

HTS CoE, Pfizer Global Research and Development, Groton, Connecticut 06340, USA.

Fluorescent detection of calcium mobilization has been used successfully to identify modulators of G-protein-coupled receptors (GPCRs); however, inherent issues with fluorescence may limit its potential for high-throughput screening miniaturization. The data presented here demonstrate that the calcium-sensitive photoprotein aequorin (AequoScreen), when compared with FLUO-4 in the same cellular background, allows for miniaturization of functional kinetic calcium flux assays, in which the rank order of potency and efficacy was maintained for a series of diverse small-molecule modulators. Small-volume (<10 microL) 384- and 1536-well aequorin assays were implemented by integration of acoustic dispensing (Echo 550) and kinetic flash luminometry (CyBi Lumax). Read More

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Digital Imaging as a Detection Method for a Fluorescent Protease Assay in 96-Well and Miniaturized Assay Plate Formats.

J Biomol Screen 1999 ;4(3):121-127

Novartis Institute of Biomedical Research, Summit, NJ.

The demand to increase throughput in HTS programs, without a concomitant addition to costs, has grown significantly during the past few years. One approach to handle this demand is assay miniaturization, which can provide greater throughput, as well as significant cost savings through reduced reagent costs. Currently, one of the major challenges facing assay miniaturization is the ability to detect the assay signal accurately and rapidly in miniaturized formats. Read More

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January 1999
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