scholarly journals High throughput flow cytometry for small molecule screening

2012 ◽  
Vol 5 (36) ◽  
pp. 968-968
Keyword(s):  
Flow Cytometry ◽  
Small Molecule ◽  
High Throughput ◽  
Small Molecule Screening

Identification of Small-Molecule Inducers of FOXP3 in Human T Cells Using High-Throughput Flow Cytometry

2017 ◽  
pp. 243-252 ◽  
Author(s):  
Rob Jepras ◽  
Poonam Shah ◽  
Metul Patel ◽  
Steve Ludbrook ◽  
Gregory Wands ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Small Molecule ◽  
High Throughput ◽  
Human T Cells

scholarly journals Identification of a Small GTPase Inhibitor Using a High-Throughput Flow Cytometry Bead-Based Multiplex Assay

2009 ◽  
Vol 15 (1) ◽  
pp. 10-20 ◽  
Author(s):  
Zurab Surviladze ◽  
Anna Waller ◽  
Yang Wu ◽  
Elsa Romero ◽  
Bruce S. Edwards ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Small Molecule ◽  
High Throughput ◽  
False Negative ◽  
Small Gtpases ◽  
Multiplex Assay ◽  
Small Gtpase ◽  
Dependent Manner ◽  
Gtp Binding

Small GTPases are key regulators of cellular activity and represent novel targets for the treatment of human diseases using small-molecule inhibitors. The authors describe a multiplex, flow cytometry bead-based assay for the identification and characterization of inhibitors or activators of small GTPases. Six different glutathione-S-transferase (GST)—tagged small GTPases were bound to glutathione beads, each labeled with a different red fluorescence intensity. Subsequently, beads bearing different GTPase were mixed and dispensed into 384-well plates with test compounds, and fluorescent—guanosine triphosphate (GTP) binding was used as the readout. This novel multiplex assay allowed the authors to screen a library of almost 200,000 compounds and identify more than 1200 positive compounds, which were further verified by dose-response analyses, using 6- to 8-plex assays. After the elimination of false-positive and false-negative compounds, several small-molecule families with opposing effects on GTP binding activity were identified. The authors detail the characterization of MLS000532223, a general inhibitor that prevents GTP binding to several GTPases in a dose-dependent manner and is active in biochemical and cell-based secondary assays. Live-cell imaging and confocal microscopy studies revealed the inhibitor-induced actin reorganization and cell morphology changes, characteristic of Rho GTPases inhibition. Thus, high-throughput screening via flow cytometry provides a strategy for identifying novel compounds that are active against small GTPases.

scholarly journals High‐Throughput Measurement of Small‐Molecule Enantiopurity by Using Flow Cytometry

ChemBioChem ◽  
2018 ◽  
Vol 19 (17) ◽  
pp. 1853-1857 ◽  
Author(s):  
Zhesen Tan ◽  
Jennifer M. Heemstra
Keyword(s):  
Flow Cytometry ◽  
Small Molecule ◽  
High Throughput

scholarly journals High-throughput small molecule screen identifies inhibitors of aberrant chromatin accessibility

2016 ◽  
Vol 113 (11) ◽  
pp. 3018-3023 ◽  
Author(s):  
Samantha G. Pattenden ◽  
Jeremy M. Simon ◽  
Aminah Wali ◽  
Chatura N. Jayakody ◽  
Jacob Troutman ◽  
...  
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Histone Deacetylase Inhibitors ◽  
A Priori ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Loss Of Function ◽  
Chromatin Signature ◽  
Biologically Relevant ◽  
Small Molecule Screening

Mutations in chromatin-modifying proteins and transcription factors are commonly associated with a wide variety of cancers. Through gain- or loss-of-function, these mutations may result in characteristic alterations of accessible chromatin, indicative of shifts in the landscape of regulatory elements genome-wide. The identification of compounds that reverse a specific chromatin signature could lead to chemical probes or potential therapies. To explore whether chromatin accessibility could serve as a platform for small molecule screening, we adapted formaldehyde-assisted isolation of regulatory elements (FAIRE), a chemical method to enrich for nucleosome-depleted genomic regions, as a high-throughput, automated assay. After demonstrating the validity and robustness of this approach, we applied this method to screen an epigenetically targeted small molecule library by evaluating regions of aberrant nucleosome depletion mediated by EWSR1-FLI1, the chimeric transcription factor critical for the bone and soft tissue tumor Ewing sarcoma. As a class, histone deacetylase inhibitors were greatly overrepresented among active compounds. These compounds resulted in diminished accessibility at targeted sites by disrupting transcription of EWSR1-FLI1. Capitalizing on precise differences in chromatin accessibility for drug discovery efforts offers significant advantages because it does not depend on the a priori selection of a single molecular target and may detect novel biologically relevant pathways.

Identification of Small-Molecule Inhibitors of RGS4 Using a High-Throughput Flow Cytometry Protein Interaction Assay

2006 ◽  
Vol 71 (1) ◽  
pp. 169-175 ◽  
Author(s):  
David L. Roman ◽  
Jeffery N. Talbot ◽  
Rebecca A. Roof ◽  
Roger K. Sunahara ◽  
John R. Traynor ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Small Molecule ◽  
High Throughput ◽  
Protein Interaction ◽  
Small Molecule Inhibitors
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