Molecular Mechanism of SSR128129E, an Extracellularly Acting, Small-Molecule, Allosteric Inhibitor of FGF Receptor Signaling (vol 23, pg 489, 2013)

© 2016 Elsevier Inc. (Cancer Cell 23, 489–501, April 15, 2013) In Figure 2F, the authors failed to highlight clearly that there is a split in the western blot (all rows) between the “0” and “0.1” condition. Even though all samples were run in the same experiment on the same blot, the image was split to remove samples that were simultaneously analyzed but irrelevant for this study. In the corrected Figure 2 F, the authors have now clearly separated both parts of the western blot. In Figure 5B, the image of the western blot showing total FGFR2 for the HEK293-FGFR2Y328D cell line was mistakenly replaced with the image of the western blot showing total FGFR2 for the HEK293-FGFR2WT cell line from Figure 5A. In the corrected Figure 5B, the authors have included the correct image of the western blot showing total FGFR2 for the HEK293-FGFR2Y328D cell line. The corrected Figure 2 and Figure 5 are included below. The authors apologize for any confusion these mistakes may have caused the readers.Correctionstatus: publishe

Molecular mechanism of SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of fgf receptor signaling

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. © 2013 Elsevier Inc