Evidence map›Paper›PMID 38714896›Full record

ArticleNature biotechnology2025

Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomics.

Stephan Eckert, Nicola Berner, Karl Kramer, Annika Schneider, Julian Müller, Severin Lechner, Sarah Brajkovic, Amirhossein Sakhteman, Christian Graetz, Jonas Fackler and 5 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

  1. Trial
  2. Preprocessing Large-Scale Proteomics Data.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Single-Injection Multi-Omics Analysis by Direct Infusion Mass Spectrometry.Angewandte Chemie (International ed. in English) · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. BRAFbioRxiv : the preprint server for biology · 2024
    Article
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

15 authors.

Stephan Eckert *Chair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany.ORCID http://orcid.org/0000-0002-6959-4439
Nicola Berner *Chair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany.
Karl KramerChair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany.ORCID http://orcid.org/0000-0003-2180-5652
Annika SchneiderChair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany.
Julian MüllerChair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany.ORCID http://orcid.org/0000-0003-4108-7926
Severin LechnerChair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany.ORCID http://orcid.org/0000-0003-2297-9208
Sarah BrajkovicChair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany.
Amirhossein SakhtemanChair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany.ORCID http://orcid.org/0000-0002-1922-6523
Christian GraetzChair of Animal Physiology and Immunology, School of Life Sciences, Technical University of Munich, Freising, Germany.ORCID http://orcid.org/0000-0002-9356-7940
Jonas FacklerInstitute of Molecular Immunology and Experimental Oncology, School of Medicine and Health, Technical University of Munich, Munich, Germany.
Michael DudekInstitute of Molecular Immunology and Experimental Oncology, School of Medicine and Health, Technical University of Munich, Munich, Germany.
Michael W PfafflChair of Animal Physiology and Immunology, School of Life Sciences, Technical University of Munich, Freising, Germany.
Percy KnolleInstitute of Molecular Immunology and Experimental Oncology, School of Medicine and Health, Technical University of Munich, Munich, Germany.
Stephanie WilhelmChair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany.
Bernhard KusterChair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany. kuster@tum.de.ORCID http://orcid.org/0000-0002-9094-1677

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) FKZ031L0168Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) FKZ161L0214ADeutsche Forschungsgemeinschaft (German Research Foundation) 325871075
6 · The paper itself

Abstract

Proteomics is making important contributions to drug discovery, from target deconvolution to mechanism of action (MoA) elucidation and the identification of biomarkers of drug response. Here we introduce decryptE, a proteome-wide approach that measures the full dose-response characteristics of drug-induced protein expression changes that informs cellular drug MoA. Assaying 144 clinical drugs and research compounds against 8,000 proteins resulted in more than 1 million dose-response curves that can be interactively explored online in ProteomicsDB and a custom-built Shiny App. Analysis of the collective data provided molecular explanations for known phenotypic drug effects and uncovered new aspects of the MoA of human medicines. We found that histone deacetylase inhibitors potently and strongly down-regulated the T cell receptor complex resulting in impaired human T cell activation in vitro and ex vivo. This offers a rational explanation for the efficacy of histone deacetylase inhibitors in certain lymphomas and autoimmune diseases and explains their poor performance in treating solid tumors.

Indexed as

ProteomeProteomicsDose-Response Relationship, DrugDrug DiscoveryHistone Deacetylase InhibitorsHumansPhenotypeT-LymphocytesHistone Deacetylase InhibitorsProteome

Identifiers

PMID38714896
PMCPMC11919725

What OpenQuestion 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 OpenQuestion graph.