Evidence map›Paper›PMID 41091880›Full record

ArticleScience advances2025

Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.

Kyosuke Shishikura, Jiasong Li, Yiming Chen, Nate R McKnight, Thomas P Keeley, Katelyn A Bustin, Eric W Barr, Snehil R Chilkamari, Mahaa Ayub, Sun Woo Kim and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Kyosuke ShishikuraDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8192-2485
Jiasong LiDepartment of Chemistry, The University of Texas at San Antonio, San Antonio, TX, USA.ORCID 0000-0003-0341-2038
Yiming ChenDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, University of Florida, Jupiter, FL, USA.ORCID 0000-0002-1311-7166
Nate R McKnightDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
Thomas P KeeleyDepartment of Physiology, Anatomy & Genetics, Target Discovery Institute, and Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0002-0334-7144
Katelyn A BustinDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8933-9825
Eric W BarrCardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Snehil R ChilkamariDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0009-5427-0683
Mahaa AyubSidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Sun Woo KimDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
Zongtao LinDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-6017-338X
Ren-Ming HuDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
Kelly HicksDepartment of Neurosurgery, Perelman School of Medicine, and Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0003-4736-3861
Xie WangDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
Donald M O'RourkeDepartment of Neurosurgery, Perelman School of Medicine, and Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-8479-7314
J Martin BollingerDepartment of Chemistry and Biochemistry and Molecular Biology, The Pennsylvania State University, State College, PA, USA.ORCID 0000-0003-0751-8585
Zev A BinderDepartment of Neurosurgery, Perelman School of Medicine, and Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-1158-231X
William H ParsonsDepartment of Chemistry and Biochemistry, Oberlin College, Oberlin, OH, USA.ORCID 0000-0001-6065-2340
Kirill A MartemyanovDepartment of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, University of Florida, Jupiter, FL, USA.ORCID 0000-0002-9925-7599
Aimin LiuDepartment of Chemistry, The University of Texas at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-4182-8176
Megan L MatthewsDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-1178-4616

Funding

Regulation of Striatal Signaling by RGS ProteinsR01DA036596 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Kirill A. Martemyanov · 2014 to 2026
$6.5M
MAOI-inspired activity probes to translate epigenetics and genetics into drugsDP1DA051620 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI MATTHEWS, MEGAN L · 2020 to 2024
$2.5M
Development and validation of an autologous mouse model for the study of immune interactions with glioblastomaR37CA285434 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Zev Ari Binder · 2024 to 2026
$2.0M
NCI NIH HHS R37 CA285434NIDA NIH HHS DP1 DA051620NIDA NIH HHS R01 DA036596
6 · The paper itself

Abstract

Hydralazine (HYZ), a treatment for preeclampsia and hypertensive crisis, is listed by the World Health Organization as an essential medicine. Its mode of action has remained unknown through its seven decades of clinical use. Here, we identify 2-aminoethanethiol dioxygenase (ADO), a key mediator of targeted protein degradation, as a selective HYZ target. The drug chelates ADO's metallocofactor and can alkylate one of its ligands. The resultant inactivation stabilizes regulators of G protein signaling (RGS4 and RGS5) that ADO normally marks for proteolysis, explaining the drug's vasodilatory activity and comporting with observations of diminished RGS levels in both clinical preeclampsia and a mouse model thereof. Its inhibition of ADO suggested use of HYZ against glioblastoma (GBM); indeed, a single dose robustly senesces cultured GBM cells. By establishing ADO as a nexus for GBM and preeclampsia and connecting it to HYZ, the results create opportunities for directed tailoring of the old drug for new therapies.

Indexed as

Enzyme InhibitorsGlioblastomaHydralazinePre-EclampsiaAnimalsCell Line, TumorDisease Models, AnimalFemaleHumansMicePregnancyEnzyme InhibitorsHydralazine

Identifiers

PMID41091880
PMCPMC12526720

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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.