Evidence map›Paper›PMID 38303712›Full record

ArticleiScience2024

Profiling of ERBB receptors and downstream pathways reveals selectivity and hidden properties of ERBB4 antagonists.

Lukša Popović, Jan P Wintgens, Yuxin Wu, Ben Brankatschk, Sascha Menninger, Carsten Degenhart, Niels Jensen, Sven P Wichert, Bert Klebl, Moritz J Rossner and 1 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

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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

11 authors at 3 institutions in 2 countries.

Lukša PopovićResearch Group Cell Signalling, Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstrasse 7, 80336 Munich, Germany.
Jan P WintgensResearch Group Cell Signalling, Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstrasse 7, 80336 Munich, Germany.
Yuxin WuResearch Group Cell Signalling, Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstrasse 7, 80336 Munich, Germany.
Ben BrankatschkSystasy Bioscience GmbH, Balanstrasse 6, 81669 Munich, Germany.
Sascha MenningerLead Discovery Center GmbH, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany.
Carsten DegenhartLead Discovery Center GmbH, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany.
Niels JensenSection of Molecular Neurobiology, Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstrasse 7, 80336 Munich, Germany.
Sven P WichertSystasy Bioscience GmbH, Balanstrasse 6, 81669 Munich, Germany.
Bert KleblLead Discovery Center GmbH, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany.
Moritz J RossnerSystasy Bioscience GmbH, Balanstrasse 6, 81669 Munich, Germany.
Michael C WehrResearch Group Cell Signalling, Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstrasse 7, 80336 Munich, Germany.
LMU Klinikum · DELead Discovery Center (Germany) · DEBioscience Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

ERBB receptor tyrosine kinases are involved in development and diseases like cancer, cardiovascular, neurodevelopmental, and mental disorders. Although existing drugs target ERBB receptors, the next generation of drugs requires enhanced selectivity and understanding of physiological pathway responses to improve efficiency and reduce side effects. To address this, we developed a multilevel barcoded reporter profiling assay, termed 'ERBBprofiler', in living cells to monitor the activity of all ERBB targets and key physiological pathways simultaneously. This assay helps differentiate on-target therapeutic effects from off-target and off-pathway side effects of ERBB antagonists. To challenge the assay, eight established ERBB antagonists were profiled. Known effects were confirmed, and previously uncharacterized properties were discovered, such as pyrotinib's preference for ERBB4 over EGFR. Additionally, two lead compounds selectively targeting ERBB4 were profiled, showing promise for clinical trials. Taken together, this multiparametric profiling approach can guide early-stage drug development and lead to improved future therapeutic interventions.

Indexed as

BiochemistryBiological sciencesCell biologyNatural sciencesPharmacology

Identifiers

PMID38303712
PMCPMC10831936
OpenAlexW4391489598

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.