ArticleBiopolymers2014
Structure-activity relationships of peptidomimetics that inhibit PPI of HER2-HER3.
Article in Biopolymers, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- An Orally Available Grafted Peptide Targeting Epidermal Growth Factor Receptor Dimers Reduces Non-Small Cell Lung Cancer Tumors in Mouse Models.ACS pharmacology & translational science · 2025Article
- Extensive conformational and physical plasticity protects HER2-HER3 tumorigenic signaling.Cell reports · 2022Article
- Molecular Targeting of Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR).Molecules (Basel, Switzerland) · 2021Review
- Article
- Design of novel lipidated peptidomimetic conjugates for targeting EGFR heterodimerization in HER2 + cancer.Bioorganic & medicinal chemistry letters · 2018Article
- Using Peptidomimetics and Constrained Peptides as Valuable Tools for Inhibiting Protein⁻Protein Interactions.Molecules (Basel, Switzerland) · 2018Review
- Design of cyclic and d-amino acids containing peptidomimetics for inhibition of protein-protein interactions of HER2-HER3.Journal of peptide science : an official publication of the European Peptide Society · 2018Article
- Homo- and Heterodimerization of Proteins in Cell Signaling: Inhibition and Drug Design.Advances in protein chemistry and structural biology · 2018Review
- A peptidomimetic with a chiral switch is an inhibitor of epidermal growth factor receptor heterodimerization.Oncotarget · 2017Article
- Targeting kinase signaling pathways with constrained peptide scaffolds.Pharmacology & therapeutics · 2017Review
- Characterizing the Hot Spots Involved in RON-MSPβ Complex Formation UsingAdvanced pharmaceutical bulletin · 2017Article
- Expression and purification of HER2 extracellular domain proteins in Schneider2 insect cells.Protein expression and purification · 2016Article
- Targeting of the epidermal growth factor receptor with mesoporphyrin IX-peptide conjugates.Journal of porphyrins and phthalocyanines · 2016Article
- Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors.Molecules (Basel, Switzerland) · 2015Review
- Novel Peptidomimetics for Inhibition of HER2:HER3 Heterodimerization in HER2-Positive Breast Cancer.Chemical biology & drug design · 2015Article
- Current and future targeted therapies for non-small-cell lung cancers with aberrant EGF receptors.Future oncology (London, England) · 2015Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Human epidermal growth factor receptor-2 (HER2) is a tyrosine kinase family protein receptor that is known to undergo heterodimerization with other members of the family of epidermal growth factor receptors (EGFR) for cell signaling. Overexpression of HER2 and deregulation of signaling has implications in breast, ovarian, and lung cancers. We have designed several peptidomimetics to block the HER2-mediated dimerization, resulting in antiproliferative activity for cancer cells. In this work, we have investigated the structure-activity relationships of peptidomimetic analogs of Compound 5. Compound 5 was conformationally constrained by N- and C-terminal modification and cyclization as well as by substitution with d-amino acids at the N-and C-termini. Among the compounds studied in this work, a peptidomimetic Compound 21 with d-amino acid substitution and its N- and C-termini capped with acetyl and amide functional groups and a reversed sequence compared to that of Compound 5 exhibited better antiproliferative activity in HER2-overexpressed breast, ovarian, and lung cancer cell lines. Compound 21 was further evaluated for its protein-protein interaction (PPI) inhibition ability using enzyme fragment complementation assay, proximity ligation assay, and Western blot analysis. Results suggested that Compound 21 is able to block HER2:HER3 interaction and inhibit phosphorylation of the kinase domain of HER2. The mode of binding of Compound 21 to HER2 protein was modeled using a docking method. Compound 21 seems to bind to domain IV of HER2 near the PPI site of EGFR:HER2, and HER:HER3 and inhibit PPI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.