Evidence map›Paper›PMID 26051217›Full record

ArticleChemistry & biology2015

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4.

Jing Lu, Yimin Qian, Martha Altieri, Hanqing Dong, Jing Wang, Kanak Raina, John Hines, James D Winkler, Andrew P Crew, Kevin Coleman and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 572 papers.

0numbers the graph read from it
0cells of the map it votes in
572citing papers in PubMed
30.0field-weighted citation impact, top 1% of its field
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

572 citing papers in PubMed, 1,116 citations in OpenAlex.

  1. PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026
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512 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Jing LuArvinas, Inc., New Haven, CT 06511, USA.
Yimin QianArvinas, Inc., New Haven, CT 06511, USA.
Martha AltieriArvinas, Inc., New Haven, CT 06511, USA.
Hanqing DongArvinas, Inc., New Haven, CT 06511, USA.
Jing WangArvinas, Inc., New Haven, CT 06511, USA.
Kanak RainaArvinas, Inc., New Haven, CT 06511, USA.
John HinesDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
James D WinklerArvinas, Inc., New Haven, CT 06511, USA.
Andrew P CrewArvinas, Inc., New Haven, CT 06511, USA.
Kevin ColemanArvinas, Inc., New Haven, CT 06511, USA.
Craig M CrewsDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA; Department of Chemistry, Yale University, New Haven, CT 06511, USA; Department of Pharmacology, Yale University, New Haven, CT 06511, USA. Electronic address: craig.crews@yale.edu.
Arvinas (United States) · USYale University · US

Funding

A MULTIPRONGED, PROTEIN DEGRADATION-BASED APPROACH TO INHIBIT HIV TRANSMISSIONR01AI084140 · NIAID · YALE UNIVERSITY · PI CREWS, CRAIG M · 2009 to 2012
$1.8M
NIAID NIH HHS AI084140NIAID NIH HHS R01 AI084140
6 · The paper itself

Abstract

BRD4, a bromodomain and extraterminal domain (BET) family member, is an attractive target in multiple pathological settings, particularly cancer. While BRD4 inhibitors have shown some promise in MYC-driven malignancies such as Burkitt's lymphoma (BL), we show that BRD4 inhibitors lead to robust BRD4 protein accumulation, which may account for their limited suppression of MYC expression, modest antiproliferative activity, and lack of apoptotic induction. To address these limitations we designed ARV-825, a hetero-bifunctional PROTAC (Proteolysis Targeting Chimera) that recruits BRD4 to the E3 ubiquitin ligase cereblon, leading to fast, efficient, and prolonged degradation of BRD4 in all BL cell lines tested. Consequently, ARV-825 more effectively suppresses c-MYC levels and downstream signaling than small-molecule BRD4 inhibitors, resulting in more effective cell proliferation inhibition and apoptosis induction in BL. Our findings provide strong evidence that cereblon-based PROTACs provide a better and more efficient strategy in targeting BRD4 than traditional small-molecule inhibitors.

Indexed as

AcetanilidesAdaptor Proteins, Signal TransducingApoptosisAzepinesBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorCell ProliferationHeterocyclic Compounds, 3-RingHumansNuclear ProteinsPeptide HydrolasesProto-Oncogene Proteins c-mycSignal TransductionThalidomideTranscription FactorsAcetanilidesAdaptor Proteins, Signal TransducingARV-825AzepinesBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsCRBN protein, humanHeterocyclic Compounds, 3-Ring(+)-JQ1 compoundNuclear ProteinsOTX015Peptide HydrolasesProto-Oncogene Proteins c-mycThalidomideTranscription FactorsTriazolesUbiquitin-Protein Ligases

Identifiers

PMID26051217
PMCPMC4475452
OpenAlexW1488181101

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.