ArticleBritish journal of pharmacology2013
A novel macrolide/fluoroketolide, solithromycin (CEM-101), reverses corticosteroid insensitivity via phosphoinositide 3-kinase pathway inhibition.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
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.
Who cites it
30 citing papers in PubMed, 80 citations in OpenAlex.
- Clarithromycin Modulates Neutrophilic Inflammation Induced byAntibiotics (Basel, Switzerland) · 2024Article
- The Molecular Blueprint for Chronic Obstructive Pulmonary Disease (COPD): A New Paradigm for Diagnosis and Therapeutics.Oxidative medicine and cellular longevity · 2023Review
- Progression of the PI3K/Akt signaling pathway in chronic obstructive pulmonary disease.Frontiers in pharmacology · 2023Review
- Cryptotanshinone Reverses Corticosteroid Insensitivity by Inhibition of Phosphoinositide-3-Kinase-δ in Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2023Article
- Clinical implications of asthma endotypes and phenotypes.Allergy and asthma proceedings · 2022Article
- Identification and treatment of T2-low asthma in the era of biologics.ERJ open research · 2021Review
- Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation.Scientific reports · 2021Article
- Role of Histone Deacetylases in Monocyte Function in Health and Chronic Inflammatory Diseases.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Progress in the mechanism and targeted drug therapy for COPD.Signal transduction and targeted therapy · 2020Review
- Theophylline and dexamethasone in combination reduce inflammation and prevent the decrease in HDAC2 expression seen in monocytes exposed to cigarette smoke extract.Experimental and therapeutic medicine · 2020Article
- PI3K inhibitor treatment ameliorates the glucocorticoid insensitivity of PBMCs in severe asthma.Clinical and translational medicine · 2020Article
- Erythromycin Suppresses the Cigarette Smoke Extract-Exposed Dendritic Cell-Mediated Polarization of CD4Journal of immunology research · 2020Article
- Cathelicidin LL-37 restoring glucocorticoid function in smoking and lipopolysaccharide-induced airway inflammation in rats.Chinese medical journal · 2019Article
- Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model.Tuberculosis and respiratory diseases · 2018Article
- The Potential for Emerging Microbiome-Mediated Therapeutics in Asthma.Current allergy and asthma reports · 2017Review
- Nature nurtures the design of new semi-synthetic macrolide antibiotics.The Journal of antibiotics · 2017Review
- Macrolides: a promising pharmacologic therapy for chronic obstructive pulmonary disease.Therapeutic advances in respiratory disease · 2017Review
- Advanced Role of Neutrophils in Common Respiratory Diseases.Journal of immunology research · 2017Review
- Pathological Roles of Neutrophil-Mediated Inflammation in Asthma and Its Potential for Therapy as a Target.Journal of immunology research · 2017Review
- Solithromycin: A Novel Fluoroketolide for the Treatment of Community-Acquired Bacterial Pneumonia.Drugs · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeCorticosteroid insensitivity is a major therapeutic problem for some inflammatory diseases including chronic obstructive pulmonary disease (COPD), and it is known to be induced by reduced histone deacetylase (HDAC)-2 activities via activation of the phosphoinositide 3-kinase (PI3K) pathway. The aim of this study is to evaluate effects of a novel macrolide/fluoroketolide, solithromycin (SOL, CEM-101), on corticosteroid sensitivity induced by oxidative stress. EXPERIMENTAL APPROACH: Corticosteroid sensitivity was determined by IC50/EC50 of dexamethasone (Dex) on TNF-α-induced CXCL8 production in U937 monocytic cell line and peripheral blood mononuclear cells (PBMC) from COPD patients. Activities of HDAC and protein phosphatase 2A (PP2A) were measured by fluorescence-based assay in cells exposed to hydrogen peroxide (H2O2). We also investigated steroid insensitive airway neutrophilia in cigarette smoke exposed mice in vivo. KEY
resultsSOL (10 μM) restored Dex sensitivity in PBMC from COPD patients, H2O2-treated U937 cells and phorbol 12-myristate 13-acetate-differentiated U937 cells. In addition, SOL restored HDAC activity with concomitant inhibition of Akt phosphorylation as surrogate marker of PI3K activation. The inhibition of Akt phosphorylation by SOL was due to increased PP2A phosphatase activity, which was reduced in COPD and oxidative stress model. Other known macrolides, such as eryhthromycin, clarithromycin and azithromycin, were significantly less effective in these responses. In cigarette smoke-exposed mice, SOL (100 mg kg(-1), po) showed significant but weak inhibition of neutrophilia, whereas Dex (10 mg kg(-1), p.o.) showed no such effect. However, a combination of SOL and Dex inhibited neutrophilia by over 50%. CONCLUSIONS AND IMPLICATIONS: SOL has potential as novel therapy for corticosteroid-insensitive diseases such as COPD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.