Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells

Staberg, Mikkel; Riemer, Christian; Xu, Rui; Dmytriyeva, Oksana; Bock, Elisabeth; Berezin, Vladimir

doi:10.1007/s13402-013-0128-6

Cited by 2 publications

(2 citation statements)

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“…Since the dimerization arm plays a major role in the stabilization of the extracellular receptor dimer, multiple mimics were previously designed [ 17 – 21 ]. As an alternative strategy to covalently constrain the dimerization arm, we utilized cycloaddition chemistry to introduce a 1,4-disubstituted [ 1 , 2 , 3 ]-triazolyl-containing bridge between the terminal residues of the sequence.…”

Section: Resultsmentioning

confidence: 99%

“…1 ) [ 2 , 16 ]. The dimerization arm is a promising target for the design of ErbB disruptors and has been validated by the development of various compounds including pertuzumab, a monoclonal antibody that targets the dimerization arm of ErbB2, as well as a peptide dendrimer that targets this site on EGFR [ 17 , 18 ]. Additionally, an unconstrained peptide mimicking the ErbB3 dimerization arm and a disulfide-bridged peptide mimicking the EGFR dimerization arm were both shown to inhibit EGFR dimerization and phosphorylation [ 19 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Inhibiting EGFR Dimerization Using Triazolyl-Bridged Dimerization Arm Mimics

et al. 2015

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The epidermal growth factor receptor (EGFR) is overexpressed in multiple carcinomas and is the focus of a variety of targeted therapies. Here we report the design of peptide-based compounds that mimic the EGFR dimerization arm and inhibit allosteric activation of EGFR. These peptides are modified to contain a triazolyl bridge between the peptide strands to constrain the EGFR dimerization arm β-loop. In this study, we demonstrate that these peptides have significantly improved proteolytic stability over the non-modified peptide sequence, and their inhibitory effects are dependent on the number of the methylene units and orientation of the introduced triazolyl bridge. We identified a peptide, EDA2, which downregulates receptor phosphorylation and dimerization and reduces cell viability. This is the first example of a biologically active triazolyl-bridged peptide targeting the EGFR dimerization interface that effectively downregulates EGFR activation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibiting EGFR Dimerization Using Triazolyl-Bridged Dimerization Arm Mimics

et al. 2015

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A Peptide Antagonist of ErbB Receptors, Inherbin3, Induces Neurite Outgrowth from Rat Cerebellar Granule Neurons Through ErbB1 Inhibition

Pankratova

Christiansen

et al. 2013

Neurochem Res

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ErbB receptors not only function in cancer, but are also key developmental regulators in the nervous system. We previously identified an ErbB1 peptide antagonist, Inherbin3, that is capable of inhibiting tumor growth in vitro and in vivo. In this study, we found that inhibition of ErbB1 kinase activity and activation of ErbB4 by NRG-1β induced neurite extension, suggesting that ErbB1 and ErbB4 act as negative and positive regulators, respectively, of the neuritogenic response. Inherbin3, inhibited activation not only of ErbB1 but also of ErbB4 in primary neurons, strongly induced neurite outgrowth in rat cerebellar granule neurons, indicating that this effect mainly was due to inhibition of ErbB1 activation.

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Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells

Abstract: Targeting the ErbB1 receptor dimerization interface is a promising strategy to inhibit receptor activation in ErbB1-expressing glioma cells.

Cited by 2 publications

References 53 publications

Inhibiting EGFR Dimerization Using Triazolyl-Bridged Dimerization Arm Mimics

Inhibiting EGFR Dimerization Using Triazolyl-Bridged Dimerization Arm Mimics

A Peptide Antagonist of ErbB Receptors, Inherbin3, Induces Neurite Outgrowth from Rat Cerebellar Granule Neurons Through ErbB1 Inhibition

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