Title: Molecular Mechanism of SSR128129E, an Extracellularly Acting, Small-Molecule, Allosteric Inhibitor of FGF Receptor Signaling
Authors: Herbert, Corentin ×
Schieborr, Ulrich
Saxena, Krishna
Juraszek, Jarek
De Smet, Frederik
Alcouffe, Chantal
Bianciotto, Marc
Saladino, Giorgio
Sibrac, David
Kudlinzki, Denis
Sreeramulu, Sridhar
Brown, Alan
Rigon, Patrice
Herault, Jean-Pascal
Lassalle, Gilbert
Blundell, Tom L
Rousseau, Frederic
Gils, Ann
Schymkowitz, Joost
Tompa, Peter
Herbert, Jean-Marc
Carmeliet, Peter
Gervasio, Francesco Luigi
Schwalbe, Harald
Bono, Françoise #
Issue Date: Apr-2013
Publisher: Cell Press
Series Title: Cancer Cell vol:23 issue:4 pages:489-501
Article number: S1535-6108(13)00074-3
Abstract: The fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling network plays an important role in cell growth, survival, differentiation, and angiogenesis. Deregulation of FGFR signaling can lead to cancer development. Here, we report an FGFR inhibitor, SSR128129E (SSR), that binds to the extracellular part of the receptor. SSR does not compete with FGF for binding to FGFR but inhibits FGF-induced signaling linked to FGFR internalization in an allosteric manner, as shown by crystallography studies, nuclear magnetic resonance, Fourier transform infrared spectroscopy, molecular dynamics simulations, free energy calculations, structure-activity relationship analysis, and FGFR mutagenesis. Overall, SSR is a small molecule allosteric inhibitor of FGF/FGFR signaling, acting via binding to the extracellular part of the FGFR.
ISSN: 1535-6108
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
Therapeutic and Diagnostic Antibodies (+)
× corresponding author
# (joint) last author

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