The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index.
FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system
Open accessAbstract
FTY720 (fingolimod) is a first‐in‐class sphingosine 1‐phosphate (S1P) receptor modulator that was highly effective in Phase II clinical trials for Multiple Sclerosis (MS). FTY720 is phosphorylated in vivo by sphingosine kinase‐2 to form the active moiety FTY720‐phosphate that binds to four of the five G protein‐coupled S1P receptor subtypes. Studies using conditional S1P1 receptor‐deficient and sphingosine kinase‐deficient mice showed that the egress of lymphocytes from lymph nodes requires signalling of lymphocytic S1P1 receptors by the endogenous ligand S1P. The S1P mimetic FTY720‐phosphate causes internalization and degradation of cell membrane‐expressed S1P1, thereby antagonizing S1P action at the receptor. In models of human MS and demyelinating polyneuropathies, functional antagonism of lymphocytic S1P1 slows S1P‐driven egress of lymphocytes from lymph nodes, thereby reducing the numbers of autoaggressive TH17 cells that recirculate via lymph and blood to the central nervous system and the sciatic/ischiatic nerves. Based on its lipophilic nature, FTY720 crosses the blood–brain barrier, and ongoing experiments suggest that the drug also down‐modulates S1P1 in neural cells/astrocytes to reduce astrogliosis, a phenomenon associated with neurodegeneration in MS. This may help restore gap‐junctional communication of astrocytes with neurons and cells of the blood–brain barrier. Additional effects may result from (down‐) modulation of S1P3 in astrocytes and of S1P1 and S1P5 in oligodendrocytes. In conclusion, FTY720 may act through immune‐based and central mechanisms to reduce inflammation and support structural restoration of the central nervous system parenchyma. Beyond the autoimmune indications, very recent studies suggest that short‐term, low‐dose administration of FTY720 could help treat chronic (viral) infections. Differential effects of the drug on the trafficking of naïve, central memory and effector memory T cell subsets are discussed.
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
1 retracted
Transient FTY720 treatment promotes immune-mediated clearance of a chronic viral infection
Premenko‐Lanier, M., Moseley, N. B., Pruett, S. T., Romagnoli, P. A., & Altman, J. D. (2008) · Nature · doi:10.1038/nature07199 · Cited by 25
RetractedTwo subsets of memory T lymphocytes with distinct homing potentials and effector functions
Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846 · cited 3×
“…antigen-specific, long-lived memory T cells preferentially home to non-lymphoid tissue where they can proliferate in response to IL-7 and IL-15 (Sallusto et al., 1999; Masopust et al., 2001; Tan et al., 2002), and that CD8 cells isolated from such tissues exhibit direct cytolytic activity ex…”
BackgroundCentral Memory and Effector Memory T Cell Subsets: Function, Generation, and Maintenance
Sallusto, F., Geginat, J., & Lanzavecchia, A. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104702 · Cited by 3,067
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-citationPreferential Localization of Effector Memory Cells in Nonlymphoid Tissue
Masopust, D., Vezys, V., Marzo, A. L., & Lefrançois, L. (2001) · Science · doi:10.1126/science.1058867 · Cited by 1,952 · cited 5×
“Earlier reports had already shown that antigen-specific, long-lived memory T cells preferentially home to non-lymphoid tissue where they can proliferate in response to IL-7 and IL-15 (Sallusto et al., 1999; Masopust et al., 2001; Tan et al., 2002), and that CD8 cells isolated from such tissues exhibit direct cytolytic…”
BackgroundInfluentialGuide 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
Kebir, H., Kreymborg, K., Ifergan, I., Dodelet-Devillers, A., Cayrol, R., Bernard, M., Giuliani, F., Arbour, N., Becher, B., & Prat, A. (2007) · Nature Medicine · doi:10.1038/nm1651 · Cited by 1,759
Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists
Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., Thornton, R., Shei, G.-J., Card, D., Keohane, C., et al. (2002) · Science · doi:10.1126/science.1070238 · Cited by 1,690
The Immune Modulator FTY720 Targets Sphingosine 1-Phosphate Receptors
Brinkmann, V., Davis, M. D., Heise, C. E., Albert, R., Cottens, S., Hof, R., Bruns, C., Prieschl, E., Baumruker, T., Hiestand, P., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200176200 · Cited by 1,504
Self-citationCD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs
Shiow, L. R., Rosen, D. B., Brdičková, N., Xu, Y., An, J., Lanier, L. L., Cyster, J. G., & Matloubian, M. (2006) · Nature · doi:10.1038/nature04606 · Cited by 1,189
Cited by
Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis
Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., & Burtin, P. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3248 · Cited by 1,273
Self-citationKappos, 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
An update on the biology of sphingosine 1-phosphate receptors
Blaho, V. A., & Hla, T. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r046300 · Cited by 516
All roads lead to PP 2A: exploiting the therapeutic potential of this phosphatase
Sangodkar, J., Farrington, C. C., McClinch, K., Galsky, M. D., Kastrinsky, D. B., & Narla, G. (2016) · The FEBS Journal · doi:10.1111/febs.13573 · Cited by 312
Lopes Pinheiro, M. A., Kooij, G., Mizee, M. R., Kamermans, A., Enzmann, G., Lyck, R., Schwaninger, M., Engelhardt, B., & de Vries, H. E. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.10.018 · Cited by 247
Metadata
- Authors
- Brinkmann, V.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2009-10-20
- Volume
- 158
- Issue
- 5
- Pages
- 1173-1182
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- OpenAlex
- W2059921365
- Cited by
- 438
- References
- 83
- FWCI
- 27.34
- 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: FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system. https://app.cochat.ai/papers/10.1111/j.1476-5381.2009.00451.x
- The paper
- Brinkmann, V. (2009). FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system. British Journal of Pharmacology. https://doi.org/10.1111/j.1476-5381.2009.00451.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.
