A time‐resolved live cell imaging assay to identify small molecule inhibitors of FGF2 signaling

Autor: David W. Will, Walter Nickel, Carlo A. Beretta, Mennatallah Ahmed, Cyril Legrand, Joe Lewis, Peter Sehr, Hans-Michael Müller, Sabine Wegehingel, Ana Yagüe Relimpio, Alina Muschko
Rok vydání: 2019
Předmět:
Cell Survival
Angiogenesis
Biophysics
Fibroblast growth factor
Biochemistry
Small Molecule Libraries
Neuroblastoma
03 medical and health sciences
Structural Biology
Live cell imaging
Cell Line
Tumor
Genetics
medicine
Humans
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Molecular Biology
Cell survival
Cell Proliferation
030304 developmental biology
0303 health sciences
Dose-Response Relationship
Drug
integumentary system
Chemistry
Cell growth
030302 biochemistry & molecular biology
Cell Biology
medicine.disease
Receptors
Fibroblast Growth Factor
Small molecule
biological factors
Cell biology
Gene Expression Regulation
Neoplastic
Leukemia
Drug Resistance
Neoplasm
embryonic structures
Fibroblast Growth Factor 2
Drug Screening Assays
Antitumor
biological phenomena
cell phenomena
and immunity
Antagonism
Signal Transduction
Zdroj: FEBS Letters. 593:2162-2176
ISSN: 1873-3468
0014-5793
DOI: 10.1002/1873-3468.13462
Popis: Fibroblast growth factor 2 (FGF2) is a cell survival factor with crucial functions in tumor-induced angiogenesis. Here, we describe a novel time-resolved FGF2 signaling assay based upon live cell imaging of neuroblastoma cells. To validate this system, we tested 8960 small molecules for inhibition of FGF2 signaling with kinetic resolution. Hit compounds were validated in dose-response experiments for FGF2 signaling, FGF receptor antagonism, downstream ERK phosphorylation and FGF2-dependent chemoresistance in a cellular leukemia model system. The new screening system for FGF2 signaling inhibitors has unique features, deselecting compounds with pleiotropic effects on cell proliferation and, along with the experimental pipeline reported, great potential for the discovery of new classes of FGF2 signaling inhibitors that block FGF2 dependent tumor cell survival.
Databáze: OpenAIRE
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