Evidence map›Paper›PMID 40629953›Full record

ArticleArchiv der Pharmazie2025

DCAF16-Based Covalent Molecular Glues for Targeted Protein Degradation of Histone Deacetylases.

Tao Sun, Shiyang Zhai, Stephan Lepper, Beate König, Mateo Malenica, Irina Honin, Finn K Hansen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Archiv der Pharmazie, 2025. 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

7 authors.

Tao SunDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Shiyang ZhaiDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Stephan LepperDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Beate KönigDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Mateo MalenicaDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Irina HoninDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Finn K HansenDepartment of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, Bonn, Germany.ORCID https://orcid.org/0000-0001-9765-5975

Funding

S.L. and F.K.H. acknowledge financial support from the Deutsche Forschungsgemeinschaft (HA 7783/4-1). T.S. (grant no. 202107060004) and S.Z. (grant no. 202106150022) are funded by the China Scholarship Council. The new NMR console for the 500-MHz NMR spectrometer used in this research was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under project number 507275896. M.M. and F.K.H. acknowledge financial support from the Deutsche Forschungsgemeinschaft (HA 7783/5-1). The work of M.M., I.H., and F.K.H. is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - GRK2873 (494832089).
6 · The paper itself

Abstract

Histone deacetylases (HDACs) are intriguing cancer targets due to their high expression in many tumors. Consequently, inhibition or degradation of HDACs can be beneficial for cancer therapy. Targeted protein degradation using molecular glues represents a promising therapeutic approach, enabling the specific degradation of numerous disease-causing proteins. However, the rational design of molecular glues in a target-based manner remains challenging. A recent study has described the identification of a DCAF16-based covalent linker-less chemical handle for molecular glues. This covalent warhead can be attached to protein of interest ligands to induce the targeted degradation of various protein classes. Inspired by this, we designed and synthesized a new class of DCAF16-based covalent molecular glues utilizing different zinc-binding groups for the targeted degradation of HDACs. This approach led to the discovery of an efficient molecular glue (10a) that reduced HDAC1 levels in multiple myeloma MM.1S cells in a potent and preferential manner.

Indexed as

Antineoplastic AgentsHistone Deacetylase 1Histone Deacetylase InhibitorsHistone DeacetylasesMultiple MyelomaCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansMolecular StructureProteolysisStructure-Activity RelationshipAntineoplastic AgentsHDAC1 protein, humanHistone Deacetylase 1Histone Deacetylase InhibitorsHistone DeacetylasescancerDCAF16histone deacetylases (HDACs)molecular gluestargeted protein degradation (TPD)

Identifiers

PMID40629953
PMCPMC12238837

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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.