Evidence map›Paper›PMID 40835825›Full record

ArticleNature communications2025

Unbiased mapping of cereblon neosubstrate landscape by high-throughput proteomics.

Martin Steger, Gisele Nishiguchi, Qiong Wu, Bjoern Schwalb, Bachuki Shashikadze, Kevin McGowan, Marisa Actis, Anup Aggarwal, Zhe Shi, Jeanine Price and 11 more

Abstract read
In one paragraph

Article in Nature communications, 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. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Proteomics-Driven Strategies for Proximity-Inducing Drug Discovery.Angewandte Chemie (International ed. in English) · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
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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

21 authors.

Martin Steger *NEOsphere Biotechnologies GmbH, Martinsried, Germany.
Gisele Nishiguchi *Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0003-2253-9325
Qiong Wu *Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0002-6063-0800
Bjoern Schwalb *NEOsphere Biotechnologies GmbH, Martinsried, Germany.
Bachuki ShashikadzeNEOsphere Biotechnologies GmbH, Martinsried, Germany.
Kevin McGowanDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Marisa ActisDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Anup AggarwalDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Zhe ShiDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0009-0008-5640-5177
Jeanine PriceDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Anand MayasundariDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Lei YangDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0002-3060-0790
Anastasia H BednarzNEOsphere Biotechnologies GmbH, Martinsried, Germany.
Sophie MachataNEOsphere Biotechnologies GmbH, Martinsried, Germany.
Tobias GraefNEOsphere Biotechnologies GmbH, Martinsried, Germany.
Denis BartoschekNEOsphere Biotechnologies GmbH, Martinsried, Germany.
Vadim DemichevDepartment of Biochemistry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Uli OhmayerNEOsphere Biotechnologies GmbH, Martinsried, Germany.ORCID http://orcid.org/0000-0003-0438-0410
Jun YangDepartment of Surgery, St. Jude Children's Research Hospital, Memphis, TN, USA. jun.yang2@stjude.org.ORCID http://orcid.org/0000-0002-0770-9659
Henrik DaubNEOsphere Biotechnologies GmbH, Martinsried, Germany. henrik.daub@neospherebiotech.com.ORCID http://orcid.org/0009-0003-0039-0870
Zoran RankovicDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA. zoran.rankovic@icr.ac.uk.ORCID http://orcid.org/0000-0001-6866-4290

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9M
EXPLORE AND TARGET THE EPIGENETIC VULNERABILITY OF PAX3-FOXO1-DRIVEN RHABDOMYOSARCOMAR01CA266600 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Xiang Chen, Jun Yang · 2022 to 2026
$3.4M
Development of small molecules to target KDM4BR01CA229739 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHEN, TAOSHENG, DAVIDOFF, ANDREW M · 2018 to 2021
$1.6M
Targetable epigenetic modifiers that promote neuroblastoma malignancy and plasticityR01CA289881 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Kevin W. Freeman, Jun Yang · 2025 to 2026
$1.4M
NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA229739NCI NIH HHS R01 CA266600NCI NIH HHS R01 CA289881
6 · The paper itself

Abstract

Molecular glue degraders (MGDs) are small molecules that co-opt the ubiquitin-proteasome system to induce degradation of target proteins, including those considered undruggable. Their discovery remains challenging due to the lack of rational design strategies and limited throughput of unbiased proteome-wide screening approaches. To address this gap, we develop a high-throughput proteomics platform based on label-free, data-independent acquisition mass spectrometry (DIA-MS), enabling integrated proteomics and ubiquitinomics profiling. Screening a diverse set of 100 cereblon (CRBN)-recruiting ligands on this platform leads to identification of a broad array of novel degraders and neosubstrates. Subsequent hit validation and structure-degradation relationship analyses guided by global proteomics reveal highly selective and potent phenyl glutarimide-based degraders targeting previously uncharacterized neosubstrates such as KDM4B, G3BP2 and VCL; none of which contain the classical CRBN β-hairpin degron. These findings underscore the power of unbiased high-throughput proteomics in MGD drug discovery and reveal a substantially expanded CRBN neosubstrate landscape beyond that defined by classical immunomodulatory imid drugs (IMiDs).

Indexed as

Adaptor Proteins, Signal TransducingProteomicsDrug DiscoveryHEK293 CellsHigh-Throughput Screening AssaysHumansLigandsMass SpectrometryProteolysisUbiquitin-Protein LigasesAdaptor Proteins, Signal TransducingCRBN protein, humanLigandsUbiquitin-Protein Ligases

Identifiers

PMID40835825
PMCPMC12368047

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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.