Trial reportBritish journal of pharmacology2012
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Trial report in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 3 of them syntheses that pooled it.
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
135 citing papers in PubMed, 3 syntheses or guidelines pooled it, 302 citations in OpenAlex.
- Sphingosine 1-phosphate (S1P) receptor modulators as an induction and maintenance therapy for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Pooled it
- Siponimod for multiple sclerosis.The Cochrane database of systematic reviews · 2021Pooled it
- Safety of S1P Modulators in Patients with Immune-Mediated Diseases: A Systematic Review and Meta-Analysis.Drug safety · 2021Pooled it
- Etrasimod Treatment Modulates Circulating and Lymph Node-Derived Lymphocytes in Crohn's Disease.International journal of molecular sciences · 2026Trial
- Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn's Disease.Digestive diseases and sciences · 2024Trial
- Icanbelimod (CBP-307), a next-generation Sphingosine-1-phosphate receptor modulator, in healthy men: pharmacokinetics, pharmacodynamics, safety, and tolerability in a randomized trial in Australia.Frontiers in immunology · 2024Trial
- Effect of siponimod on magnetic resonance imaging measures of neurodegeneration and myelination in secondary progressive multiple sclerosis: Gray matter atrophy and magnetization transfer ratio analyses from the EXPAND phase 3 trial.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Trial
- Single-dose of LC51-0255, a selective S1PClinical and translational science · 2022Trial
- Cost Effectiveness and Budget Impact of Siponimod Compared to Interferon Beta-1a in the Treatment of Adult Patients with Secondary Progressive Multiple Sclerosis with Active Disease in Switzerland.PharmacoEconomics · 2021Trial
- First-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple oral doses of SAR247799, a selective G-protein-biased sphingosine-1 phosphate receptor-1 agonist for endothelial protection.British journal of clinical pharmacology · 2021Trial
- Population Pharmacokinetic Analysis of BMS-986166, a Novel Selective Sphingosine-1-Phosphate-1 Receptor Modulator, and Exposure-Response Assessment of Lymphocyte Counts and Heart Rate in Healthy Participants.Clinical pharmacology in drug development · 2021Trial
- Effect of the sphingosine-1-phosphate receptor modulator ozanimod on leukocyte subtypes in relapsing MS.Neurology(R) neuroimmunology & neuroinflammation · 2020Trial
- Siponimod pharmacokinetics, safety, and tolerability in combination with the potent CYP3A4 inhibitor itraconazole in healthy subjects with different CYP2C9 genotypes.European journal of clinical pharmacology · 2019Trial
- Effect of Fluconazole Coadministration and CYP2C9 Genetic Polymorphism on Siponimod Pharmacokinetics in Healthy Subjects.Clinical pharmacokinetics · 2019Trial
- Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study.Clinical pharmacology in drug development · 2018Trial
- Cardiac effects of amiselimod compared with fingolimod and placebo: results of a randomised, parallel-group, phase I study in healthy subjects.British journal of clinical pharmacology · 2017Trial
- Amiselimod, a novel sphingosine 1-phosphate receptor-1 modulator, has potent therapeutic efficacy for autoimmune diseases, with low bradycardia risk.British journal of pharmacology · 2017Trial
- Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.British journal of clinical pharmacology · 2013Trial
- Intracerebral Hemorrhage Induces Monocyte TNF Signaling in Patients That Is Suppressed by BAF312.Annals of clinical and translational neurology · 2026Article
- Structural insights into subtype-specific agonist recognition by sphingosine-1-phosphate receptors.PLoS biology · 2026Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeBAF312 is a next-generation sphingosine 1-phosphate (S1P) receptor modulator, selective for S1P(1) and S1P(5 ) receptors. S1P(1) receptors are essential for lymphocyte egress from lymph nodes and a drug target in immune-mediated diseases. Here, we have characterized the immunomodulatory potential of BAF312 and the S1P receptor-mediated effects on heart rate using preclinical and human data. EXPERIMENTAL APPROACH: BAF312 was tested in a rat experimental autoimmune encephalomyelitis (EAE) model. Electrophysiological recordings of G-protein-coupled inwardly rectifying potassium (GIRK) channels were carried out in human atrial myocytes. A Phase I multiple-dose trial studied the pharmacokinetics, pharmacodynamics and safety of BAF312 in 48 healthy subjects. KEY
resultsBAF312 effectively suppressed EAE in rats by internalizing S1P(1) receptors, rendering them insensitive to the egress signal from lymph nodes. In healthy volunteers, BAF312 caused preferential decreases in CD4(+) T cells, T(naïve) , T(central memory) and B cells within 4-6 h. Cell counts returned to normal ranges within a week after stopping treatment, in line with the elimination half-life of BAF312. Despite sparing S1P(3) receptors (associated with bradycardia in mice), BAF312 induced rapid, transient (day 1 only) bradycardia in humans. BAF312-mediated activation of GIRK channels in human atrial myocytes can fully explain the bradycardia. CONCLUSION AND IMPLICATIONS: This study illustrates species-specific differences in S1P receptor specificity for first-dose cardiac effects. Based on its profound but rapidly reversible inhibition of lymphocyte trafficking, BAF312 may have potential as a treatment for immune-mediated diseases.
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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.