ArticleBritish journal of pharmacology2009
Pharmacological characterization of PF-00547659, an anti-human MAdCAM monoclonal antibody.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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
36 citing papers in PubMed, 68 citations in OpenAlex.
- Efficacy and Safety of the Anti-mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn's Disease.Journal of Crohn's & colitis · 2024Trial
- Long-Term Safety and Efficacy of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Monoclonal Antibody Ontamalimab (SHP647) for the Treatment of Crohn's Disease: The OPERA II Study.Inflammatory bowel diseases · 2022Trial
- Long-term Safety and Efficacy of the Anti-MAdCAM-1 Monoclonal Antibody Ontamalimab [SHP647] for the Treatment of Ulcerative Colitis: The Open-label Study TURANDOT II.Journal of Crohn's & colitis · 2021Trial
- Molecular Profiling of Ulcerative Colitis Subjects from the TURANDOT Trial Reveals Novel Pharmacodynamic/Efficacy Biomarkers.Journal of Crohn's & colitis · 2019Trial
- Trial
- Anti-MAdCAM Antibody Increases ß7+ T Cells and CCR9 Gene Expression in the Peripheral Blood of Patients With Crohn's Disease.Journal of Crohn's & colitis · 2018Trial
- Clinical pharmacology of AMG 181, a gut-specific human anti-α4β7 monoclonal antibody, for treating inflammatory bowel diseases.British journal of clinical pharmacology · 2014Trial
- A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis.Gut · 2013Trial
- Long-Term Safety of Ontamalimab in Patients with Moderate to Severe Inflammatory Bowel Disease.Clinical and experimental gastroenterology · 2026Article
- The Pathogenesis of Inflammatory Bowel Diseases.The Surgical clinics of North America · 2025Review
- [Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti Integrins].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2024Review
- Horizon scanning: new and future therapies in the management of inflammatory bowel disease.eGastroenterology · 2023Review
- Targeting Leukocyte Trafficking in Inflammatory Bowel Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Article
- Optogenetic activation of local colonic sympathetic innervations attenuates colitis by limiting immune cell extravasation.Immunity · 2021Article
- Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives.Clinical and experimental gastroenterology · 2021Review
- Emerging treatments for inflammatory bowel disease.Therapeutic advances in chronic disease · 2020Review
- Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: the OPERA study.Intestinal research · 2020Article
- MAdCAM-1-Mediated Intestinal Lymphocyte Homing Is Critical for the Development of Active Experimental Autoimmune Encephalomyelitis.Frontiers in immunology · 2019Article
- Effect of PF-00547659 on Central Nervous System Immune Surveillance and Circulating β7+ T Cells in Crohn's Disease: Report of the TOSCA Study.Journal of Crohn's & colitis · 2018Article
- Frontiers in Drug Research and Development for Inflammatory Bowel Disease.Frontiers in pharmacology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe adhesion molecule mucosal addressin cell adhesion molecule (MAdCAM) plays an essential role in the recruitment of lymphocytes to specialized high endothelial venules of the gastrointestinal tract and in their excessive tissue extravasation observed in inflammatory conditions, such as Crohn's disease. We have characterized the in vitro pharmacological properties of two monoclonal antibodies blocking MAdCAM, MECA-367 and PF-00547659, and determined their pharmacokinetic/pharmacodynamic profiles in vivo. EXPERIMENTAL APPROACH: Functional adhesion assays and surface plasmon resonance were used to characterize, in vitro, the pharmacological properties of MECA-367 and PF-00547659. The in vivo effects of MECA-367 and PF-00547659 on restriction of beta(7) (+) memory T lymphocytes were determined in mice and macaques, respectively, over the pharmacological dose range to confirm pharmacokinetic/pharmacodynamic relationships. KEY
resultsMECA-367 and PF-00547659 bound with high affinity to mouse and human MAdCAM with K(d) values of 5.1 and 16.1 pmol.L(-1) respectively and blocked the adhesion of alpha(4)beta(7) (+) leukocytes to MAdCAM with similar potency. MECA-367 and PF-00547659 induced a similar, dose-dependent two- to threefold increase in circulating populations of beta(7) (+) memory T-cells in the mouse and macaque; without affecting the beta(7) (-) populations. CONCLUSIONS AND IMPLICATIONS: PF-00547659 has potential utility in the treatment of inflammatory conditions by blocking tissue homing of activated alpha(4)beta(7) (+) leukocytes. The characterization of a rodent cross-reacting antibody as a surrogate for PF-00547659 in the search for potential pharmacological biomarkers and the determination of efficacious doses was effective in addressing the restricted orthologous cross-reactivity of PF-00547659 and the challenges this poses with respect to efficacy and safety testing.
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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.