Evidence map›Paper›PMID 40759792›Full record

ArticleEMBO molecular medicine2025

Development of a novel therapy for systolic heart failure.

Corey Pollock, Xilun Wang, Hussam Alsaraji, Joseph Menassa, George Mbogo, Dimuthu Angage, Benjamin Richards, Jason Glab, Keshava K Datta, Liana Theodoridis and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

Corey PollockDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.
Xilun WangDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.
Hussam AlsarajiDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.
Joseph MenassaDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.
George MbogoDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.
Dimuthu AngageDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.ORCID http://orcid.org/0009-0009-4776-487X
Benjamin RichardsDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.
Jason GlabDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.
Keshava K DattaResearch Platforms, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.ORCID http://orcid.org/0000-0002-4322-5491
Liana TheodoridisDepartment of Microbiology, Anatomy and Physiology, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.ORCID http://orcid.org/0000-0001-8271-8689
Steve PetrovskiDepartment of Microbiology, Anatomy and Physiology, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.ORCID http://orcid.org/0000-0002-6304-6853
Daniel DonnerBaker Heart and Diabetes Institute, 75 Commercial Road, Victoria, 3004, Australia.ORCID http://orcid.org/0000-0003-4924-720X
Yuvixza Lizarme-SalasDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.
Xiao-Jun DuBaker Heart and Diabetes Institute, 75 Commercial Road, Victoria, 3004, Australia.ORCID http://orcid.org/0000-0001-5213-3911
Michael FoleyDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.
Brian J SmithDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia.
Belinda AbbottDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia. b.abbott@latrobe.edu.au.
Hamsa PuthalakathDepartment of Biochemistry and Chemistry, La Trobe University, Kingsbury Drive, Bundoora, Vic, 3086, Australia. h.puthalakath@latrobe.edu.au.ORCID http://orcid.org/0000-0001-5178-1175

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Heart failure presents a critical health challenge with a 5-year mortality rate of up to 50%. Conventional treatments often lead to bradycardia or hypotension due to their impact on patient hemodynamics. To address this issue, we utilized high-throughput drug screening combined with structure-activity relationship-based medicinal chemistry to develop a novel drug-like compound that effectively blocks the β-adrenergic receptor (β-AR) mediated apoptosis pathway. This compound demonstrated both safety and efficacy in pre-clinical mouse models without adversely affecting cardiac output. Through thermal proteome profiling mass spectrometry, we identified the compound's target as Wdr3, a regulator of the Hippo signaling pathway. This target identification was further validated using CRISPR-based knockout experiments. Our findings provide a valuable framework for the development of hemodynamically neutral therapies aimed at treating systolic heart failure.

Indexed as

Adrenergic beta-AntagonistsHeart Failure, SystolicAnimalsApoptosisDisease Models, AnimalHigh-Throughput Screening AssaysHumansMiceReceptors, Adrenergic, betaSignal TransductionAdrenergic beta-AntagonistsReceptors, Adrenergic, betaApoptosisBimHFPKAβ-AR

Identifiers

PMID40759792
PMCPMC12423297

What OpenQuestion holds

Textmetadata
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.