Herbert, Corentin and Schieborr, Ulrich and Saxena, Krishna and Tompa, Péter (2013) Molecular mechanism of SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of fgf receptor signaling. CANCER CELL, 23 (4). pp. 489-501. ISSN 1535-6108
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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. © 2013 Elsevier Inc.
Item Type: | Article |
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Uncontrolled Keywords: | structure activity relation; SIGNAL TRANSDUCTION; priority journal; nuclear magnetic resonance; MUTAGENESIS; Molecular dynamics; internalization; infrared spectroscopy; human cell; human; drug protein binding; drug binding; Crystallography; controlled study; Cell Survival; Cell growth; Cell Differentiation; ARTICLE; ANGIOGENESIS; allosterism; unclassified drug; ssr 128129e; fibroblast growth factor receptor; epidermal growth factor receptor kinase inhibitor; antineoplastic agent |
Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia |
SWORD Depositor: | MTMT SWORD |
Depositing User: | MTMT SWORD |
Date Deposited: | 05 Nov 2013 09:47 |
Last Modified: | 05 Nov 2013 09:47 |
URI: | http://real.mtak.hu/id/eprint/7129 |
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