Structural Characterization of the Interaction of the Fibroblast Growth Factor Receptor with a Small Molecule Allosteric Inhibitor.

Authors :: Kappert F
Sreeramulu S
Jonker HRA
Richter C
Rogov VV
Proschak E
Hargittay B
Saxena K
Schwalbe H
Source :: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2018 Jun 04; Vol. 24 (31), pp. 7861-7865. Date of Electronic Publication: 2018 May 03.
Publication Year :: 2018
Abstract: The interaction of fibroblast growth factors (FGFs) with their fibroblast growth factor receptors (FGFRs) are important in the signaling network of cell growth and development. SSR128129E (SSR), a ligand of small molecular weight with potential anti-cancer properties, acts allosterically on the extracellular domains of FGFRs. Up to now, the structural basis of SSR binding to the D3 domain of FGFR remained elusive. This work reports the structural characterization of the interaction of SSR with one specific receptor, FGFR3, by NMR spectroscopy. This information provides a basis for rational drug design for allosteric FGFR inhibitors.<br /> (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Subjects :: Allosteric Regulation
Drug Design
Molecular Docking Simulation
Protein Binding
Receptors, Fibroblast Growth Factor chemistry
Structure-Activity Relationship
Thermodynamics
Antineoplastic Agents chemistry
Indolizines chemistry
Protein Kinase Inhibitors chemistry
Receptors, Fibroblast Growth Factor antagonists & inhibitors
ortho-Aminobenzoates chemistry

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