Evidence map›Paper›PMID 42209806›Full record

ArticleNature chemical biology2026

Pharmacological targeting of IRF4 as a therapeutic strategy for multiple myeloma.

Michael P Agius, Chen Song, Qi Liu, Tomoki Iemura, Laura Hevenor, N Connor Payne, Romanos Sklavenitis Pistofidis, Lorena Pantano, Hongfang Zhao, Hyuk-Soo Seo and 11 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 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. Interferon regulatory factors orchestrate CD8International journal of molecular medicine · 2026
    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

21 authors.

Michael P Agius *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Chen Song *Department of Medicine, Harvard Medical School, Boston, MA, USA.
Qi LiuDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Tomoki IemuraDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Laura HevenorDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
N Connor PayneCenter for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.
Romanos Sklavenitis PistofidisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Lorena PantanoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Hongfang ZhaoDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Hyuk-Soo SeoChemical Biology Program, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0646-2102
Daniel Heilpern-MalloryDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4296-015X
Caleb HeaslipDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Zhen-Yu J SunDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Puspalata BashyalDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Michelle P AranhaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8230-5726
Elizabeth LightbodyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Ralph MazitschekCenter for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1105-689X
Sirano Dhe-PaganonChemical Biology Program, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0824-5929
Constantine S MitsiadesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2321-8005
Irene M GhobrialDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. irene_ghobrial@dfci.harvard.edu.ORCID http://orcid.org/0000-0001-7361-3092
Jun QiDepartment of Medicine, Harvard Medical School, Boston, MA, USA. jun_qi@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-1461-3356

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Interferon regulatory factor 4 (IRF4) is an oncogenic transcription factor (TF) in several hematological malignancies. To date, no pharmacological agents have been developed specifically for IRF4 due to the challenging nature of targeting TFs. Here we first identified (S)-H1, a binder of IRF4, by targeting the SPI1-IRF4 interaction on IRF4's interferon association domain via high-throughput screening. Next, we successfully turned our binder into dIRF4-2, a first-in-class proteolysis-targeting chimera of IRF4, by linking (S)-H1 to E3 ligase ligands of cereblon. dIRF4-2 can induce highly selective proteasomal degradation of IRF4 and has strong cytotoxic effects in all multiple myeloma lines evaluated in vitro. Our study showcases methodology to effectively target the IRF family of TFs and illustrates how to convert an inert binder into a powerful chemical probe for studying the functions of important oncoproteins that are structurally difficult to target.

Identifiers

PMID42209806

What OpenQuestion holds

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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.