Evidence map›Paper›PMID 38654248›Full record

ArticleRespiratory research2024

PI3Kγδ inhibition suppresses key disease features in a rat model of asthma.

James W Pinkerton, Silvia Preite, Antonio Piras, Dimitrios Zervas, Thomais Markou, Mark S Freeman, Tobias Hofving, Emil Ivarsson, Sara J Bonvini, Wayne Brailsford and 3 more

Open access · goldAbstract read
In one paragraph

Article in Respiratory research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.8field-weighted citation impact, top 24% of its field
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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Role of GLCCI1 in inhibiting PI3K-induced NLRP3 inflammasome activation in asthma.Chinese medical journal pulmonary and critical care medicine · 2024
    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

13 authors at 2 institutions in 2 countries.

James W PinkertonEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Silvia PreiteEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Antonio PirasEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Dimitrios ZervasEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Thomais MarkouEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Mark S FreemanEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Tobias HofvingEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Emil IvarssonEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Sara J BonviniEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Wayne BrailsfordEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Linda YrlidEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Maria G BelvisiEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden.
Mark A BirrellEarly Respiratory & Immunology, Biopharmaceuticals R&D AstraZeneca, Gothenburg, Sweden. mark.birrell@astrazeneca.com.
AstraZeneca (Sweden) · SEImperial College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTwo isoforms of Phosphoinositide 3-kinase (PI3K), p110γ and p110δ, are predominantly expressed in leukocytes and represent attractive therapeutic targets for the treatment of allergic asthma. The study aim was to assess the impact of administration of an inhaled PI3Kγδ inhibitor (AZD8154) in a rat model of asthma.

methodsFirstly, we checked that the tool compound, AZD8154, inhibited rat PI3K γ & δ kinases using rat cell-based assays. Subsequently, a time-course study was conducted in a rat model of asthma to assess PI3K activity in the lung and how it is temporally associated with other key transcription pathways and asthma like features of the model. Finally, the impact on lung dosed AZD8154 on target engagement, pathway specificity, airway inflammation and lung function changes was assessed.

resultsData showed that AZD8154 could inhibit rat PI3K γ & δ isoforms and, in a rat model of allergic asthma the PI3K pathway was activated in the lung. Intratracheal administration of AZD8154 caused a dose related suppression PI3K pathway activation (reduction in pAkt) and unlike after budesonide treatment, STAT and NF-κB pathways were not affected by AZD8154. The suppression of the PI3K pathway led to a marked inhibition of airway inflammation and reduction in changes in lung function.

conclusionThese data show that a dual PI3Kγδ inhibitor suppress key features of disease in a rat model of asthma to a similar degree as budesonide and indicate that dual PI3Kγδ inhibition may be an effective treatment for people suffering from allergic asthma.

Indexed as

AsthmaDisease Models, AnimalAnimalsAnti-Asthmatic AgentsClass Ib Phosphatidylinositol 3-KinaseClass I Phosphatidylinositol 3-KinasesDose-Response Relationship, DrugLungMaleOvalbuminPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsRatsRats, Sprague-DawleyAnti-Asthmatic AgentsClass Ib Phosphatidylinositol 3-KinaseClass I Phosphatidylinositol 3-KinasesOvalbuminPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsPhosphoinositide 3-kinase P110γδ asthma AZD8154

Identifiers

PMID38654248
PMCPMC11040934
OpenAlexW4395024718

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.