Trial reportBritish journal of clinical pharmacology2014
Pharmacokinetics and pharmacodynamics of the cathepsin S inhibitor, LY3000328, in healthy subjects.
Trial report in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed.
- First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP1617, a Cathepsin-S Inhibitor, in Healthy Adult Subjects.Clinical and translational science · 2026Trial
- CTSS regulates macrophage lipid metabolic reprogramming and white matter repair after intracerebral hemorrhage.Journal of translational medicine · 2026Article
- Cathepsin S: a double-edged protease in barrier damage, neuroimmune inflammation, and tissue repair, with implications for dermatology.Frontiers in immunology · 2026Review
- Probing the activity of cysteine cathepsins in inflammatory bowel diseases.Scientific reports · 2025Article
- Brain-cervical lymph node crosstalk contributes to brain injury induced by subarachnoid hemorrhage in mice.Nature communications · 2025Article
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Cathepsin S: molecular mechanisms in inflammatory and immunological processes.Frontiers in immunology · 2025Review
- Antibody-peptide conjugates deliver covalent inhibitors blocking oncogenic cathepsins.Nature chemical biology · 2024Article
- Multicenter proteome-wide Mendelian randomization study identifies causal plasma proteins in melanoma and non-melanoma skin cancers.Communications biology · 2024Article
- Structural Modifications of Covalent Cathepsin S Inhibitors: Impact on Affinity, Selectivity, and Permeability.ACS medicinal chemistry letters · 2024Article
- Water channel protein AQP1 in cytoplasm is a critical factor in breast cancer local invasion.Journal of experimental & clinical cancer research : CR · 2023Article
- Imbalanced IL-37/TNF-α/CTSS signaling disrupts corneal epithelial barrier in a dry eye model in vitro.The ocular surface · 2022Article
- Cathepsin S as a potential therapeutic target for chronic pain.Medicine in drug discovery · 2020Article
- Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics.Respiratory research · 2020Review
- Inhibition of Cathepsin S Reduces Lacrimal Gland Inflammation and Increases Tear Flow in a Mouse Model of Sjögren's Syndrome.Scientific reports · 2019Article
- PP2A: A Novel Target to Prevent Cathepsin S-mediated Damage in Smoking-induced Chronic Obstructive Pulmonary Disease.American journal of respiratory and critical care medicine · 2019Article
- Increased Cathepsin S activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in Sjögren's Syndrome patients.Scientific reports · 2018Article
- Cysteine Protease Cathepsins in Atherosclerotic Cardiovascular Diseases.Journal of atherosclerosis and thrombosis · 2018Review
- Cathepsin S As an Inhibitor of Cardiovascular Inflammation and Calcification in Chronic Kidney Disease.Frontiers in cardiovascular medicine · 2017Review
- Engineered nanomaterial-induced lysosomal membrane permeabilization and anti-cathepsin agents.Journal of toxicology and environmental health. Part B, Critical reviews · 2017Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe aim of this study was to assess the safety and tolerability, pharmacokinetics and pharmacodynamics of LY3000328 when administered as single escalating doses to healthy volunteers.
methodsThis was a phase 1, placebo-controlled, dose escalation study with LY3000328 in 21 healthy male volunteers. Subjects were administered escalating LY3000328 doses up to 300 mg with food in this single dose study. Blood samples were collected at set times post-dose for the assessment of LY3000328 pharmacokinetics and the measurement of cathepsin S (CatS) activity, CatS mass and calculated CatS specific activity.
resultsAll doses of LY3000328 were well tolerated, with linear pharmacokinetics up to the 300 mg dose. The pharmacodynamic activity of LY3000328 was measured ex vivo showing a biphasic response to LY3000328, where CatS activity declines, then returns to baseline, and then increases to a level above baseline. CatS mass was also assessed post-dose which increased in a dose-dependent manner, and continued to increase after LY3000328 had been cleared from the body. CatS specific activity was additionally calculated to normalize CatS activity for changes in CatS mass. This demonstrated the increase in CatS activity was attributable to the increase in CatS mass detected in plasma.
conclusionA specific inhibitor of CatS which is cleared quickly from plasma may produce a transient decrease in plasma CatS activity which is followed by a more prolonged increase in plasma CatS mass which may have implications for the future clinical development of inhibitors of CatS.
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