The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
The selective sphingosine 1‐phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species‐specific effects on heart rate
Open accessAbstract
BACKGROUND AND PURPOSE: BAF312 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 RESULTS: BAF312 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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
Matloubian, M., Lo, C. G., Cinamon, G., Lesneski, M. J., Xu, Y., Brinkmann, V., Allende, M. L., Proia, R. L., & Cyster, J. G. (2004) · Nature · doi:10.1038/nature02284 · Cited by 2,581
Self-citationGuide to receptors and channels (GRAC), 5th edition
Alexander, S., Mathie, A., & Peters, J. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01649_1.x · Cited by 1,947
Guidelines for reporting experiments involving animals: the ARRIVE guidelines
McGrath, J., Drummond, G., McLachlan, E., Kilkenny, C., & Wainwright, C. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00873.x · Cited by 1,592
Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs
Cyster, J. G. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115628 · Cited by 856
Human eosinophil chemotaxis and selective in vivo recruitment by sphingosine 1-phosphate
Roviezzo, F., Del Galdo, F., Abbate, G., Bucci, M., D'Agostino, B., Antunes, E., De Dominicis, G., Parente, L., Rossi, F., Cirino, G., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401439101 · Cited by 100
Cited by
Kappos, L., Bar-Or, A., Cree, B. A. C., Fox, R. J., Giovannoni, G., Gold, R., Vermersch, P., Arnold, D. L., Arnould, S., Scherz, T., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30475-6 · Cited by 942
Self-citationTargeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond
Kunkel, G. T., Maceyka, M., Milstien, S., & Spiegel, S. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4099 · Cited by 434
Scott, F. L., Clemons, B., Brooks, J., Brahmachary, E., Powell, R., Dedman, H., Desale, H. G., Timony, G. A., Martinborough, E., Rosen, H., et al. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13476 · Cited by 308
Comi, G., Kappos, L., Selmaj, K. W., Bar-Or, A., Arnold, D. L., Steinman, L., Hartung, H.-P., Montalban, X., Kubala Havrdová, E., Cree, B. A. C., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30239-x · Cited by 285
Vascular and immunobiology of the circulatory sphingosine 1-phosphate gradient
Yanagida, K., & Hla, T. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021014-071635 · Cited by 109
Metadata
- Authors
- Gergely, P., Nuesslein‐Hildesheim, B., Guerini, D., Brinkmann, V, Traebert, M., Bruns, C., Pan, S., Gray, N., Hinterding, K., Cooke, N., Groenewegen, A., Vitaliti, A., Sing, T., Luttringer, O., Yang, J., Gardin, A., Wang, N., Crumb Jr, W., Saltzman, M., Rosenberg, M., & Wallström, E.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2012-10-08
- Volume
- 167
- Issue
- 5
- Pages
- 1035-1047
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- OpenAlex
- W1493585689
- Cited by
- 305
- References
- 5
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: The selective sphingosine 1‐phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species‐specific effects on heart rate. https://app.cochat.ai/papers/10.1111/j.1476-5381.2012.02061.x
- The paper
- Gergely, P., Nuesslein‐Hildesheim, B., Guerini, D., Brinkmann, V, Traebert, M., Bruns, C., Pan, S., Gray, N., Hinterding, K., Cooke, N., Groenewegen, A., Vitaliti, A., Sing, T., Luttringer, O., Yang, J., Gardin, A., Wang, N., Crumb Jr, W., Saltzman, M., . . . Wallström, E. (2012). The selective sphingosine 1‐phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species‐specific effects on heart rate. British Journal of Pharmacology. https://doi.org/10.1111/j.1476-5381.2012.02061.x
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
