Evidence mapPaperPMID 30314880Full record

ArticleBioorganic & medicinal chemistry letters2018

Design of novel lipidated peptidomimetic conjugates for targeting EGFR heterodimerization in HER2 + cancer.

Himgauri Naik, Ted Gauthier, Sitanshu Singh, Seetharama Jois

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 39% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Peptidomimetics in cancer targeting.Molecular medicine (Cambridge, Mass.) · 2022
    Review
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Himgauri NaikSchool of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, United States.
Ted GauthierBiotechnology Laboratory, LSU AgCenter, Louisiana State University, Baton Rouge, LA 70803, United States.
Sitanshu SinghSchool of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, United States.
Seetharama JoisSchool of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, United States. Electronic address: jois@ulm.edu.
University of Louisiana at Monroe · USLouisiana State University Agricultural Center · US

Funding

NCI NIH HHS R15 CA188225
6 · The paper itself

Abstract

The human epidermal growth factor receptor (EGFR) family is known to be involved in cell signaling pathways. The extracellular domain of EGFR consists of four domains, of which domain II and domain IV are known to be involved in the dimerization process. Overexpression of these receptors is known to play a significant role in heterodimerization of these receptors leading to the development of cancer. We have designed peptidomimetic molecules to inhibit the EGFR heterodimerization interaction that have shown antiproliferative activity and specificity for HER2-positive cancer cell lines. Among these, a peptidomimetic, compound 5, exhibited antiproliferative activity at low nanomolar concentrations in HER2-overexpressing cancer cell lines. To improve the stability of this peptidomimetic, we have designed and synthesized a novel conjugate of peptidomimetic compound 5 with a lipid, stearic acid. The antiproliferative activity of this conjugate was evaluated in HER2-positive cancer cell lines. Results suggested that the conjugate exhibited selective antiproliferative activity in HER2-overexpressing breast and lung cancer cell lines and was able to block HER2:HER3 heterodimerization. Also, the conjugate showed improved stability with a half-life of 5 h in human serum compared to the half-life of 2 h for parent compound 5. The binding affinity of the conjugate to HER2 protein was evaluated by SPR analysis, and the mode of binding of the lipid conjugate to domain IV of HER2 protein was demonstrated by docking analysis. Thus, this novel lipid conjugate can be used to target HER2-overexpressing cancers.

Indexed as

Drug DesignBinding SitesBreast NeoplasmsCell Line, TumorCell ProliferationDimerizationErbB ReceptorsFemaleHalf-LifeHumansLung NeoplasmsMolecular Docking SimulationPeptidomimeticsProtein BindingReceptor, ErbB-3Stearic AcidsEGFR protein, humanErbB ReceptorsPeptidomimeticsReceptor, ErbB-3stearic acidStearic AcidsEGFRHER2Lipid conjugationLung cancerPeptidePeptidomimeticProtein-protein interactionsStructure-activity relationshipSurface plasmon resonance

Identifiers

PMID30314880
PMCPMC6283100
OpenAlexW2894684771

What Socratic holds

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Registered trials

None linked

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 Socratic graph.