Evidence map›Paper›PMID 39803451›Full record

ArticlebioRxiv : the preprint server for biology2024

Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.

Kyosuke Shishikura, Jiasong Li, Yiming Chen, Nate R McKnight, Katelyn A Bustin, Eric W Barr, Snehil R Chilkamari, Mahaa Ayub, Sun Woo Kim, Zongtao Lin and 10 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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

5 · Who and what money

Authors and funding

20 authors.

Kyosuke ShishikuraDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
Jiasong LiDepartment of Chemistry, The University of Texas at 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.
Nate R McKnightDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
Katelyn A BustinDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
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.
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.
Ren-Ming HuDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
Kelly HicksDepartment of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Xie WangDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
Donald M O'RourkeDepartment of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
J Martin BollingerThe Pennsylvania State University, Department of Chemistry and Biochemistry and Molecular Biology, State College, PA, USA.
Zev A BinderDepartment of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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, TX, USA.ORCID 0000-0002-4182-8176
Megan L MatthewsDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.

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

The vasodilator hydralazine (HYZ) has been used clinically for ~ 70 years and remains on the World Health Organization's List of Essential Medicines as a therapy for preeclampsia. Despite its longstanding use and the concomitant progress toward a general understanding of vasodilation, the target and mechanism of HYZ have remained unknown. We show that HYZ selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating its metal cofactor and alkylating one of its ligands. This covalent inactivation slows entry of proteins into the Cys/N-degron pathway that ADO initiates. HYZ's capacity to stabilize regulators of G-protein signaling (RGS4/5) normally marked for degradation by ADO explains its effect on blood vessel tension and comports with prior associations of insufficient RGS levels with human preeclampsia and analogous symptoms in mice. The established importance of ADO in glioblastoma led us to test HYZ in these cell types. Indeed, a single treatment induced senescence, suggesting a potential new HYZ-based therapy for this deadly brain cancer.

Identifiers

PMID39803451
PMCPMC11722266

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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.