Trial reportBMC pharmacology & toxicology2013
Safety, tolerability, pharmacokinetics and pharmacodynamics of GSK2239633, a CC-chemokine receptor 4 antagonist, in healthy male subjects: results from an open-label and from a randomised study.
Trial report in BMC pharmacology & toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 22 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.
A Microdose Study to Describe the Intravenous Pharmacokinetics of [14C]-GSK2239633 in Healthy Male Subjects
A Randomised, Double-blind, Placebo-controlled, Cross-over Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Oral Doses of GSK2239633 in Healthy Male Subjects.
Who cites it
22 citing papers in PubMed.
- Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2014Trial
- Structure basis for C-C chemokine receptor 4 modulation by orthosteric and allosteric antagonists.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The CCL17/CCL22-CCR4 Axis in Pain Pathogenesis: A Comprehensive Review of Immune-Mediated Mechanisms and Therapeutic Opportunities.Molecular neurobiology · 2025Review
- Precision Medicine in Asthma: The Role of Biomarkers.ImmunoTargets and therapy · 2025Review
- Exploring an Intracellular Allosteric Site of CC-Chemokine Receptor 4 from 3D Models, Probe Simulations, and Mutagenesis.ACS pharmacology & translational science · 2024Article
- A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments.Antibodies (Basel, Switzerland) · 2024Review
- CC Chemokine Family Members' Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury-A Review of Clinical and Experimental Findings.International journal of molecular sciences · 2024Review
- CC Chemokine Receptor 4 (CCR4) as a Possible New Target for Therapy.International journal of molecular sciences · 2022Review
- Strategic, feasibility, economic, and cultural aspects of phase 0 approaches: Is it time to change the drug development process in order to increase productivity?Clinical and translational science · 2022Review
- Skin-resident dendritic cells mediate postoperative pain via CCR4 on sensory neurons.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- What does elevated TARC/CCL17 expression tell us about eosinophilic disorders?Seminars in immunopathology · 2021Review
- Review
- Phase 0/microdosing approaches: time for mainstream application in drug development?Nature reviews. Drug discovery · 2020Review
- A degradatory fate for CCR4 suggests a primary role in Th2 inflammation.Journal of leukocyte biology · 2020Article
- CCR4 Antagonists Inhibit TACS medicinal chemistry letters · 2018Article
- Targeting cytokines to treat asthma and chronic obstructive pulmonary disease.Nature reviews. Immunology · 2018Review
- Intracellular Receptor Modulation: Novel Approach to Target GPCRs.Trends in pharmacological sciences · 2018Review
- The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity.International journal of molecular sciences · 2017Review
- Discovery of AZD-2098 and AZD-1678, Two Potent and Bioavailable CCR4 Receptor Antagonists.ACS medicinal chemistry letters · 2017Article
- Targeting chemokine receptors in disease--a case study of CCR4.European journal of pharmacology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe CC-chemokine receptor 4 (CCR4) is thought potentially to play a critical role in asthma pathogenesis due to its ability to recruit type 2 T-helper lymphocytes to the inflamed airways. Therefore, CCR4 provides an excellent target for anti-inflammatory therapy.
methodsThe safety, tolerability, pharmacokinetics and pharmacodynamics of the CCR4 antagonist GSK2239633, N-(3-((3-(5-chlorothiophene-2-sulfonamido)-4-methoxy-1H-indazol-1-yl)methyl)benzyl)-2-hydroxy-2-methylpropanamide, were examined in healthy males. Two studies were performed: 1) an open-label, study in which six subjects received a single intravenous infusion of [14C]-GSK2239633 100 μg (10 kBq) (NCT01086462), and 2) a randomised, double-blind, placebo-controlled, cross-over, ascending dose study in which 24 subjects received single oral doses of GSK2239633 150-1500 mg (NCT01371812).
resultsFollowing intravenous dosing, plasma GSK2239633 displayed rapid, bi-phasic distribution and slow terminal elimination (t½: 13.5 hours), suggesting that GSK2239633 was a low to moderate clearance drug. Following oral dosing, blood levels of GSK2239633 reached Cmax rapidly (median tmax: 1.0-1.5 hours). Estimated GSK2239633 bioavailability was low with a maximum value determined of only 16%. Food increased GSK2239633 systemic exposure (as assessed by AUC and Cmax). Increases in AUC and Cmax were less than dose proportional. Adverse events were reported by three subjects (50%) following intravenous administration, and by 19 subjects (79%) following oral administration; most (46/47; 98%) events were mild/moderate in intensity. GSK2239633 1500 mg inhibited thymus- and activation-regulated chemokine-induced (TARC) actin polymerisation reaching a mean CCR4 occupancy of 74%.
conclusionIn conclusion, GSK2239633 was well-tolerated and capable of inhibiting TARC from activating the CCR4 receptor.
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.