Evidence map›Paper›PMID 38991154›Full record

ArticleJournal of medicinal chemistry2024

Targeting Myeloperoxidase Ameliorates Gouty Arthritis: A Virtual Screening Success Story.

Isaac de A Matos, Jorge L Dallazen, Lorenna R Reis, Luiz Felipe Souza, Regina C Bevevino, Rafael D de Moura, Graziella E Ronsein, Nicolas Carlos Hoch, Nivan Bezerra da Costa Júnior, Soraia Kátia P Costa and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2024. 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. Review
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

11 authors.

Isaac de A MatosDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, Brazil.
Jorge L DallazenDepartment of Pharmacology, Institute of Biological Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
Lorenna R ReisDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, Brazil.
Luiz Felipe SouzaDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, Brazil.
Regina C BevevinoDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, Brazil.
Rafael D de MouraDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, Brazil.
Graziella E RonseinDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, Brazil.
Nicolas Carlos HochDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, Brazil.
Nivan Bezerra da Costa JúniorDepartment of Chemistry, Federal University of Sergipe, São Cristóvão 49100-000, Sergipe, Brazil.
Soraia Kátia P CostaDepartment of Pharmacology, Institute of Biological Sciences, University of São Paulo, São Paulo 05508-000, Brazil.ORCID 0000-0002-2574-4490
Flavia C MeottiDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, Brazil.ORCID 0000-0002-7217-3352

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study presents a new approach for identifying myeloperoxidase (MPO) inhibitors with strong in vivo efficacy. By combining inhibitor-like rules and structure-based virtual screening, the pipeline achieved a 70% success rate in discovering diverse, nanomolar-potency reversible inhibitors and hypochlorous acid (HOCl) scavengers. Mechanistic analysis identified RL6 as a genuine MPO inhibitor and RL7 as a potent HOCl scavenger. Both compounds effectively suppressed HOCl production in cells and neutrophils, with RL6 showing a superior inhibition of neutrophil extracellular trap release (NETosis). In a gout arthritis mouse model, intraperitoneal RL6 administration reduced edema, peroxidase activity, and IL-1β levels. RL6 also exhibited oral bioavailability, significantly reducing paw edema when administered orally. This study highlights the efficacy of integrating diverse screening methods to enhance virtual screening success, validating the anti-inflammatory potential of potent inhibitors, and advancing the MPO inhibitor research.

Indexed as

Arthritis, GoutyPeroxidaseAnimalsDrug Evaluation, PreclinicalEnzyme InhibitorsHumansHypochlorous AcidMaleMiceNeutrophilsStructure-Activity RelationshipEnzyme InhibitorsHypochlorous AcidPeroxidase

Identifiers

PMID38991154
PMCPMC11284790

What OpenQuestion holds

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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.