| Literature DB >> 23597563 |
Corentin Herbert1, Ulrich Schieborr, Krishna Saxena, Jarek Juraszek, Frederik De Smet, Chantal Alcouffe, Marc Bianciotto, Giorgio Saladino, David Sibrac, Denis Kudlinzki, Sridhar Sreeramulu, Alan Brown, Patrice Rigon, Jean-Pascal Herault, Gilbert Lassalle, Tom L Blundell, Frederic Rousseau, Ann Gils, Joost Schymkowitz, Peter Tompa, Jean-Marc Herbert, Peter Carmeliet, Francesco Luigi Gervasio, Harald Schwalbe, Françoise Bono.
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.Entities:
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Year: 2013 PMID： 23597563 DOI： 10.1016/j.ccr.2013.02.018
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743