Evidence map›Paper›PMID 40532131›Full record

ArticleJournal of medicinal chemistry2025

Development and Characterization of the First Selective Class IIb Histone Deacetylase Degraders.

Shiyang Zhai, Irina Honin, Linda Schäker-Hübner, Maria Hanl, Lukas Jacobi, Finn Dressler, Dominika Ewa Pieńkowska, Philipp König, Jan Gerhartz, Rabea Voget and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. 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

17 authors.

Shiyang ZhaiDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.ORCID 0009-0005-6840-3177
Irina HoninDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.ORCID 0009-0009-7091-8419
Linda Schäker-HübnerDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.
Maria HanlDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.
Lukas JacobiInstitute of Innate Immunity, Department of Systems Immunology and Proteomics, Medical Faculty, University of Bonn, 53127 Bonn, Germany.
Finn DresslerIndividualized Pharmacotherapy, Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, 48149 Münster, Germany.
Dominika Ewa PieńkowskaInstitute of Structural Biology, Medical Faculty, University of Bonn, 53127 Bonn, Germany.
Philipp KönigDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.
Jan GerhartzInstitute of Structural Biology, Medical Faculty, University of Bonn, 53127 Bonn, Germany.ORCID 0009-0002-9457-4656
Rabea VogetDepartment of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.
Gerd BendasDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.ORCID 0000-0002-8667-7201
Michael GütschowDepartment of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.ORCID 0000-0002-9376-7897
Felix MeissnerInstitute of Innate Immunity, Department of Systems Immunology and Proteomics, Medical Faculty, University of Bonn, 53127 Bonn, Germany.
Bjoern B BurckhardtIndividualized Pharmacotherapy, Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, 48149 Münster, Germany.ORCID 0000-0002-1782-9937
Radosław P NowakInstitute of Structural Biology, Medical Faculty, University of Bonn, 53127 Bonn, Germany.ORCID 0000-0002-0605-0071
Christian SteinebachDepartment of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.ORCID 0000-0001-5638-1955
Finn K HansenDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany.ORCID 0000-0001-9765-5975

Funding

Degrading therapeutically important kinases using small moleculesR01CA218278 · NCI · STANFORD UNIVERSITY · PI Eric Sebastian Fischer, NATHANAEL Schiander GRAY · 2019 to 2026
$4.6M
The molecular basis of IMiD induced neo-substrate recruitment to the CRL4CRBN ubiquitin E3 ligase.R01CA214608 · NCI · DANA-FARBER CANCER INST · PI Eric Sebastian Fischer · 2017 to 2026
$4.0M
NCI NIH HHS R01 CA214608NCI NIH HHS R01 CA218278
6 · The paper itself

Abstract

Proteolysis-targeting chimeras (PROTACs) are emerging new therapeutic modalities that facilitate the targeted degradation of disease-relevant proteins via an event-driven mode of action. In this work, we report the design, synthesis, and biological evaluation of the first-in-class selective degraders of the class IIb histone deacetylases (HDACs) 6 and 10. To this end, the dual HDAC6/10 inhibitor tubastatin A and a ring-opened analog were connected via well-established PROTAC linkers to pomalidomide and phenylglutarimides as cereblon recruiters. This approach led to the discovery of

Indexed as

Histone Deacetylase InhibitorsHistone DeacetylasesCell Line, TumorHistone Deacetylase 6HumansProteolysisStructure-Activity RelationshipThalidomideHDAC10 protein, humanHDAC6 protein, humanHistone Deacetylase 6Histone Deacetylase InhibitorsHistone DeacetylasespomalidomideThalidomide

Identifiers

PMID40532131
PMCPMC12245577

What OpenQuestion holds

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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.