Evidence map›Paper›PMID 37455289›Full record

ArticleAngewandte Chemie (International ed. in English)2023

From Tethered to Freestanding Stabilizers of 14-3-3 Protein-Protein Interactions through Fragment Linking.

Emira J Visser, Priyadarshini Jaishankar, Eline Sijbesma, Marloes A M Pennings, Edmee M F Vandenboorn, Xavier Guillory, R Jeffrey Neitz, John Morrow, Shubhankar Dutta, Adam R Renslo and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Restoring the 14-3-3/CRAF regulatory interaction in Noonan syndrome using molecular glues.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Fragment-based drug discovery: A graphical review.Current research in pharmacology and drug discovery · 2025
    Review
  11. Targeted Protein Localization by Covalent 14-3-3 Recruitment.Journal of the American Chemical Society · 2024
    Article
  12. Article
  13. Review
  14. Development of a NanoBRET assay for evaluation of 14-3-3σ molecular glues.SLAS discovery : advancing life sciences R & D · 2024
    Article
  15. Review
  16. Article
  17. 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

13 authors at 2 institutions in 2 countries.

Emira J VisserLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Den Dolech 2, 5612, AZ Eindhoven, The Netherlands.
Priyadarshini JaishankarDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Centre (SMDC), University of California San Francisco (UCSF), San Francisco, CA, 94143, USA.
Eline SijbesmaLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Den Dolech 2, 5612, AZ Eindhoven, The Netherlands.
Marloes A M PenningsLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Den Dolech 2, 5612, AZ Eindhoven, The Netherlands.
Edmee M F VandenboornLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Den Dolech 2, 5612, AZ Eindhoven, The Netherlands.
Xavier GuilloryLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Den Dolech 2, 5612, AZ Eindhoven, The Netherlands.
R Jeffrey NeitzDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Centre (SMDC), University of California San Francisco (UCSF), San Francisco, CA, 94143, USA.
John MorrowDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Centre (SMDC), University of California San Francisco (UCSF), San Francisco, CA, 94143, USA.
Shubhankar DuttaDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Centre (SMDC), University of California San Francisco (UCSF), San Francisco, CA, 94143, USA.
Adam R RensloDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Centre (SMDC), University of California San Francisco (UCSF), San Francisco, CA, 94143, USA.
Luc BrunsveldLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Den Dolech 2, 5612, AZ Eindhoven, The Netherlands.
Michelle R ArkinDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Centre (SMDC), University of California San Francisco (UCSF), San Francisco, CA, 94143, USA.
Christian OttmannLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Den Dolech 2, 5612, AZ Eindhoven, The Netherlands.ORCID 0000-0001-7315-0315
Eindhoven University of Technology · NLUniversity of California, San Francisco · US

Funding

Systematic stabilization of specific protein-protein interactionsR01GM147696 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ARKIN, MICHELLE · 2022 to 2025
$1.4M
NIGMS NIH HHS R01 GM147696
6 · The paper itself

Abstract

Small-molecule stabilization of protein-protein interactions (PPIs) is a promising strategy in chemical biology and drug discovery. However, the systematic discovery of PPI stabilizers remains a largely unmet challenge. Herein we report a fragment-linking approach targeting the interface of 14-3-3 and a peptide derived from the estrogen receptor alpha (ERα) protein. Two classes of fragments-a covalent and a noncovalent fragment-were co-crystallized and subsequently linked, resulting in a noncovalent hybrid molecule in which the original fragment interactions were largely conserved. Supported by 20 crystal structures, this initial hybrid molecule was further optimized, resulting in selective, 25-fold stabilization of the 14-3-3/ERα interaction. The high-resolution structures of both the single fragments, their co-crystal structures and those of the linked fragments document a feasible strategy to develop orthosteric PPI stabilizers by linking to an initial tethered fragment.

Indexed as

14-3-3 ProteinsEstrogen Receptor alphaDrug DiscoveryProtein Binding14-3-3 ProteinsEstrogen Receptor alphaDrug DiscoveryFragment-Based Drug DiscoveryFragment LinkingMolecular GluesProteins

Identifiers

PMID37455289
PMCPMC11287480
OpenAlexW4384493421

What OpenQuestion holds

Textmetadata
LicenceTDM
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.