ArticleBritish journal of pharmacology2016
Neutrophil maturation rate determines the effects of dipeptidyl peptidase 1 inhibition on neutrophil serine protease activity.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- A Phase IIa, Single-Blind, Placebo-Controlled, Parallel-Group Study to Assess Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Brensocatib in Adults with Cystic Fibrosis.Clinical pharmacokinetics · 2025Trial
- Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF, a phase II randomised, double-blind, placebo-controlled, dose-finding study.The European respiratory journal · 2025Trial
- Dipeptidyl Peptidase 1 Inhibitor AZD7986 Induces a Sustained, Exposure-Dependent Reduction in Neutrophil Elastase Activity in Healthy Subjects.Clinical pharmacology and therapeutics · 2018Trial
- Epithelial desquamation observed in a phase I study of an oral cathepsin C inhibitor (GSK2793660).British journal of clinical pharmacology · 2017Trial
- The dipeptidyl peptidase 1 inhibition landscape in bronchiectasis and its future direction.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Phase III AIRTIVITY study design: verducatib (BI 1291583) in people with bronchiectasis.ERJ open research · 2026Article
- Bronchiectasis Treatment Goals, Unmet Needs, and Emerging Therapies: A Podcast.Pulmonary therapy · 2026Article
- Dipeptidyl peptidase 1 inhibitors and neutrophilic inflammation in bronchiectasis: a narrative review.Journal of thoracic disease · 2025Review
- Dipeptidyl peptidase 1 inhibitors for inflammatory respiratory diseases: mechanisms, clinical trials, and therapeutic prospects.Frontiers in pharmacology · 2025Review
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- Dipeptidyl peptidase 1 inhibition as a potential therapeutic approach in neutrophil-mediated inflammatory disease.Frontiers in immunology · 2023Review
- The pharmacokinetic profile of brensocatib and its effect on pharmacodynamic biomarkers including NE, PR3, and CatG in various rodent species.Frontiers in pharmacology · 2023Article
- An optimized method of extracting and quantifying active Neutrophil serine proteases from human whole blood cells.PloS one · 2022Article
- DPP1 Inhibitors: Exploring the Role of Water in the S2 Pocket of DPP1 with Substituted Pyrrolidines.ACS medicinal chemistry letters · 2019Article
- Premedication with a cathepsin C inhibitor alleviates early primary graft dysfunction in mouse recipients after lung transplantation.Scientific reports · 2019Article
- Neutrophil maturation rate determines the effects of dipeptidyl peptidase 1 inhibition on neutrophil serine protease activity.British journal of pharmacology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeNeutrophil serine proteases (NSPs) are activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation. The effects of neutrophil turnover rate on NSP activity following DPP1 inhibition was studied in a rat pharmacokinetic/pharmacodynamic model. EXPERIMENTAL APPROACH: Rats were treated with a DPP1 inhibitor twice daily for up to 14 days; NSP activity was measured in onset or recovery studies, and an indirect response model was fitted to the data to estimate the turnover rate of the response. KEY
resultsMaximum NSP inhibition was achieved after 8 days of treatment and a reduction of around 75% NSP activity was achieved at 75% in vitro DPP1 inhibition. Both the rate of inhibition and recovery of NSP activity were consistent with a neutrophil turnover rate of between 4-6 days. Using human neutrophil turnover rate, it is predicted that maximum NSP inhibition following DPP1 inhibition takes around 20 days in human. CONCLUSIONS AND IMPLICATIONS: Following inhibition of DPP1 in the rat, the NSP activity was determined by the amount of DPP1 inhibition and the turnover of neutrophils and is thus supportive of the role of neutrophil maturation in the activation of NSPs. Clinical trials to monitor the effect of a DPP1 inhibitor on NSPs should take into account the delay in maximal response on the one hand as well as the potential delay in a return to baseline NSP levels following cessation of treatment.
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