Evidence map›Paper›PMID 40575311›Full record

ArticleJACS Au2025

Oxidative and Hydrolytic HNO Formation from a Clinical Drug Hydroxyurea Catalyzed by Horseradish Peroxidase: Basic Mechanism, Active Site Effect, and Implications for Drug Design.

Erika McCarthy, Dariya Baizhigitova, Jia-Min Chu, Yong Zhang

Abstract read
In one paragraph

Article in JACS Au, 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

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

4 authors.

Erika McCarthyDepartment of Chemistry and Chemical Biology, Stevens Institute of Technology, 1 Castle Point Terrace, Hoboken, New Jersey 07030, United States.
Dariya BaizhigitovaDepartment of Chemistry and Chemical Biology, Stevens Institute of Technology, 1 Castle Point Terrace, Hoboken, New Jersey 07030, United States.
Jia-Min ChuDepartment of Chemistry and Chemical Biology, Stevens Institute of Technology, 1 Castle Point Terrace, Hoboken, New Jersey 07030, United States.
Yong ZhangDepartment of Chemistry and Chemical Biology, Stevens Institute of Technology, 1 Castle Point Terrace, Hoboken, New Jersey 07030, United States.ORCID https://orcid.org/0000-0001-7207-6416

Funding

Structure, Spectra, and Roles of Metal and Active Site in HNO Heme Protein CompleR15GM085774 · NIGMS · UNIVERSITY OF SOUTHERN MISSISSIPPI · PI ZHANG, YONG · 2008 to 2021
$1.4M
NIGMS NIH HHS R15 GM085774
6 · The paper itself

Abstract

HNO plays an important role in many biological processes related to vasodilation, regulation of enzyme activities, and neurological functions. The understanding of enzymatic oxidative HNO-releasing pathways in biology remains scarce. We investigated HNO formation from a well-established small-molecule drug hydroxyurea catalyzed by horseradish peroxidase (HRP). Density functional theory results reveal two sequential proton-coupled electron transfers from hydroxyurea to HRP Compound I as the most favorable mechanism for HNO generation, which was found to be kinetically feasible and thermodynamically favorable. This is consistent with its experimentally observed reactivity. Moreover, the large active site model study uncovered interesting conformation changes involving HRP's amino acid H-bonding network through the reaction pathway, which were employed to anchor the evolving substrate via its key CONH

Indexed as

density functional calculationsdrug designhydroxyureanitroxylreaction mechanism

Identifiers

PMID40575311
PMCPMC12188405

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.