Evidence map›Paper›PMID 42048443›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Restoring the 14-3-3/CRAF regulatory interaction in Noonan syndrome using molecular glues.

Johanna M Virta, Holly R Vickery, Markella Konstantinidou, Mckenna C Crawford, Marloes A M Pennings, Christian Ottmann, Luc Brunsveld, Michelle R Arkin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Johanna M VirtaDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Center, University of California, San Francisco, CA 94143.ORCID 0000-0001-9893-5565
Holly R VickeryDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Center, University of California, San Francisco, CA 94143.
Markella KonstantinidouDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Center, University of California, San Francisco, CA 94143.
Mckenna C CrawfordDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Center, University of California, San Francisco, CA 94143.
Marloes A M PenningsLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven 5600 MB, The Netherlands.
Christian OttmannLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven 5600 MB, The Netherlands.ORCID 0000-0001-7315-0315
Luc BrunsveldLaboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven 5600 MB, The Netherlands.ORCID 0000-0001-5675-511X
Michelle R ArkinDepartment of Pharmaceutical Chemistry and Small Molecule Discovery Center, University of California, San Francisco, CA 94143.ORCID 0000-0002-9366-6770

Funding

HHS | NIH | National Institute of General Medical Sciences (NIGMS) GM147696NWO | Exacte en Natuurwetenschappen (ENW) OCENW.M20.200Ono Pharma Foundation N/A
6 · The paper itself

Abstract

Noonan syndrome (NS) is the most common RASopathy, a developmental disorder that derives from dysregulation of the mitogen-activated protein kinase (MAPK) pathway. NS results from modestly activating mutations in proteins throughout the pathway. Trametinib, a MEK inhibitor, has shown promising results for certain NS complications, but NS-specific therapeutic options are lacking. CRAF activity, which is governed by the adaptor protein 14-3-3, represents a key NS regulatory node that has not been exploited. When phosphorylated (p) at CRAF S259, the 14-3-3/CRAF-pS259 complex adopts an inactive conformation in which CRAF does not fully bind to RAS or to other RAFs. NS mutations in CRAF occur at residues surrounding S259 (CRAF

Indexed as

14-3-3 ProteinsNoonan SyndromeProto-Oncogene Proteins c-rafHumansMutationPhosphorylationProtein BindingPyridonesPyrimidinones14-3-3 ProteinsProto-Oncogene Proteins c-rafPyridonesPyrimidinonestrametinib14-3-3CRAF/RAF1molecular glueNoonan syndromeprotein–protein interactions (PPI)

Identifiers

PMID42048443
PMCPMC13142914

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Registered trials

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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.