scholarly journals Cover Feature: High‐Throughput Measurement of Small‐Molecule Enantiopurity by Using Flow Cytometry (ChemBioChem 17/2018)

ChemBioChem ◽  
2018 ◽  
Vol 19 (17) ◽  
pp. 1794-1794
Author(s):  
Zhesen Tan ◽  
Jennifer M. Heemstra
Keyword(s):  
Flow Cytometry ◽  
Small Molecule ◽  
High Throughput

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

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

scholarly journals High-Throughput Flow Cytometry Identifies Small-Molecule Inhibitors for Drug Repurposing in T-ALL

2018 ◽  
Vol 23 (7) ◽  
pp. 732-741 ◽  
Author(s):  
Dominique R. Perez ◽  
Christian K. Nickl ◽  
Anna Waller ◽  
Cristina Delgado-Martin ◽  
Travis Woods ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Small Molecule ◽  
High Throughput ◽  
Kinase Inhibitors ◽  
Small Molecule Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
Drug Repurposing ◽  
Low Oxygen

Kinase inhibitors have dramatically increased patient survival in a multitude of cancers, including hematological malignancies. However, kinase inhibitors have not yet been integrated into current clinical trials for patients with T-cell-lineage acute lymphoblastic leukemia (T-ALL). In this study, we used a high-throughput flow cytometry (HTFC) approach to test a collection of small-molecule inhibitors, including 26 FDA-approved tyrosine kinase inhibitors in a panel of T-ALL cell lines and patient-derived xenografts. Because hypoxia is known to cause resistance to chemotherapy, we developed a synthetic niche that mimics the low oxygen levels found in leukemic bone marrow to evaluate the effects of hypoxia on the tested inhibitors. Drug sensitivity screening was performed using the Agilent BioCel automated liquid handling system integrated with the HyperCyt HT flow cytometry platform, and the uptake of propidium iodide was used as an indication of cell viability. The HTFC dose–response testing identified several compounds that were efficacious in both normal and hypoxic conditions. This study shows that some clinically approved kinase inhibitors target T-ALL in the hypoxic niche of the bone marrow.

Integration of Virtual Screening with High-Throughput Flow Cytometry to Identify Novel Small Molecule Formylpeptide Receptor Antagonists

2005 ◽  
Vol 68 (5) ◽  
pp. 1301-1310 ◽  
Author(s):  
Bruce S. Edwards ◽  
Cristian Bologa ◽  
Susan M. Young ◽  
Konstantin V. Balakin ◽  
Eric R. Prossnitz ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Virtual Screening ◽  
Small Molecule ◽  
High Throughput ◽  
Receptor Antagonists ◽  
Formylpeptide Receptor
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