Evidence map›Paper›PMID 42424456›Full record

ArticleScience (New York, N.Y.)2026

Degron-independent recruitment of KAT2A expands the target space of CRBN molecular glues.

Samuel Ojeda, Meng Wang, Kheewoong Baek, Wallace Bourgeois, Alba Sommerschield, Hong Yue, Rebecca J Metivier, Panos Karagiannis, Talya S Levitz, Yuan Xiong and 3 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 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. 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.

Samuel Ojeda *Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-7121-539X
Meng Wang *Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0009-0009-9339-3096
Kheewoong BaekDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-6853-4936
Wallace BourgeoisDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-6935-8890
Alba SommerschieldDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-4833-2226
Hong YueDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0003-4347-3193
Rebecca J MetivierDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-9929-6857
Panos KaragiannisDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-6459-7561
Talya S LevitzDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-9938-7580
Yuan XiongDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-2211-8267
Katherine A DonovanDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-8539-5106
Scott A ArmstrongDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9099-4728
Eric S FischerDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-7337-6306

Funding

TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
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
Development of a generalizable chemo-proteomics screening platform for small molecule degraders applied to HDACsR01CA262188 · NCI · DANA-FARBER CANCER INST · PI FISCHER, ERIC SEBASTIAN · 2022 to 2025
$1.8M
NCI NIH HHS P01 CA066996NCI NIH HHS R01 CA214608NCI NIH HHS R01 CA218278NCI NIH HHS R01 CA262188
6 · The paper itself

Abstract

Lysine acetyltransferases (KATs) cooperate with oncogenes such as c-Myc, estrogen receptor, and lysine methyltransferase 2A (KMT2A) fusions to sustain malignant programs. Targeting of KAT proteins has shown clinical efficacy; however, achieving homolog selectivity for most KATs remains a major challenge. By extending cereblon (CRBN)-based molecular glues beyond the canonical degron space, we developed an exquisitely selective degrader of KAT2A. Cryo-electron microscopy revealed that CRBN recruits KAT2A independently of a degron; instead, the molecular glue engages a surface-exposed tyrosine, mimicking antibody-like molecular recognition. Selective KAT2A degradation leads to potent ablation of histone H3 lysine 9 acetylation (H3K9Ac), antiproliferative effects in acute myeloid leukemia cell lines, and in vivo efficacy in a patient-derived xenograft model, establishing KAT2A as a targetable vulnerability to treat a wide range of malignancies. More generally, degron-independent recruitment extends the CRBN-targetable proteome.

Indexed as

Adaptor Proteins, Signal TransducingDegronsHistone AcetyltransferasesHistone-Lysine N-MethyltransferaseMyeloid-Lymphoid Leukemia ProteinProteolysisUbiquitin-Protein LigasesAcetylationAnimalsCell Line, TumorCell ProliferationCryoelectron MicroscopyHistonesHumansLeukemia, Myeloid, AcuteMiceAdaptor Proteins, Signal TransducingCRBN protein, humanHistone AcetyltransferasesHistone-Lysine N-MethyltransferaseHistonesKMT2A protein, humanMyeloid-Lymphoid Leukemia ProteinProteolysis Targeting ChimeraTyrosineUbiquitin-Protein Ligases

Identifiers

PMID42424456
PMCPMC13423211

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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.