Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis
Abstract
The discovery of fingolimod (FTY720/Gilenya; Novartis), an orally active immunomodulatory drug, has opened up new approaches to the treatment of multiple sclerosis, the most common inflammatory disorder of the central nervous system. Elucidation of the effects of fingolimod--mediated by the modulation of sphingosine 1-phosphate (S1P) receptors--has indicated that its therapeutic activity could be due to regulation of the migration of selected lymphocyte subsets into the central nervous system and direct effects on neural cells, particularly astrocytes. An improved understanding of the biology of S1P receptors has also been gained. This article describes the discovery and development of fingolimod, which was approved by the US Food and Drug Administration in September 2010 as a first-line treatment for relapsing forms of multiple sclerosis, thereby becoming the first oral disease-modifying therapy to be approved for multiple sclerosis in the United States.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
FTY720 is a sphingosine-1-phosphate receptor agonist that blocks lymph node egress and has been shown to protect NOD mice from T1D.
“FTY720, a sphingosine-1-phosphate receptor agonist that blocks lymph node egress and has been shown to protect NOD mice from T1D21,22”
From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [22]
Cites
Two 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 · see citing works
Central 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 · see citing works
Preferential 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 · see citing works
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 · see citing works
Compston, A., & Coles, A. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08220-x · Cited by 1,743 · see citing works
Visualizing the generation of memory CD4 T cells in the whole body
Reinhardt, R. L., Khoruts, A., Merica, R., Zell, T., & Jenkins, M. K. (2001) · Nature · doi:10.1038/35065111 · Cited by 1,026 · see citing works
Phenotype and function of human T lymphocyte subsets: Consensus and issues
Appay, V., van Lier, R. A. W., Sallusto, F., & Roederer, M. (2008) · Cytometry Part A · doi:10.1002/cyto.a.20643 · Cited by 729 · see citing works
Cellular mechanisms of IL-17-induced blood-brain barrier disruption
Huppert, J., Closhen, D., Croxford, A., White, R., Kulig, P., Pietrowski, E., Bechmann, I., Becher, B., Luhmann, H. J., Waisman, A., et al. (2010) · The FASEB Journal · doi:10.1096/fj.09-141978 · Cited by 529 · see citing works
Sanna, M. G., Wang, S.-K., Gonzalez-Cabrera, P. J., Don, A., Marsolais, D., Matheu, M. P., Wei, S. H., Parker, I., Jo, E., Cheng, W.-C., et al. (2006) · Nature Chemical Biology · doi:10.1038/nchembio804 · Cited by 406 · see citing works
Kang, Z., Altuntas, C. Z., Gulen, M. F., Liu, C., Giltiay, N., Qin, H., Liu, L., Qian, W., Ransohoff, R. M., Bergmann, C., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.03.004 · Cited by 297 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Natural products as sources of new drugs over the 30 years from 1981 to 2010
Newman, D. J., & Cragg, G. M. (2012) · Journal of Natural Products · doi:10.1021/np200906s · Cited by 4,687 · see citing works
Drug repurposing: progress, challenges and recommendations
Pushpakom, S., Iorio, F., Eyers, P. A., Escott, K. J., Hopper, S., Wells, A., Doig, A., Guilliams, T., Latimer, J., McNamee, C., et al. (2019) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.168 · Cited by 4,718 · see citing works
Opportunities and challenges in phenotypic drug discovery: an industry perspective
Moffat, J. G., Vincent, F., Lee, J. A., Eder, J., & Prunotto, M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.111 · Cited by 939 · see citing works
Microglia polarization from M1 to M2 in neurodegenerative diseases
Guo, S., Wang, H., & Yin, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.815347 · Cited by 920 · see citing works
Teijaro, J. R., Walsh, K. B., Cahalan, S., Fremgen, D. M., Roberts, E., Scott, F., Martinborough, E., Peach, R., Oldstone, M. B. A., & Rosen, H. (2011) · Cell · doi:10.1016/j.cell.2011.08.015 · Cited by 688 · see citing works
Function and therapeutic value of astrocytes in neurological diseases
Lee, H.-G., Wheeler, M. A., & Quintana, F. J. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00390-x · Cited by 662 · see citing works
Liang, J., Nagahashi, M., Kim, E. Y., Harikumar, K. B., Yamada, A., Huang, W.-C., Hait, N. C., Allegood, J. C., Price, M. M., Avni, D., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2012.11.013 · Cited by 563 · see citing works
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 · see citing works
An autoimmune stem-like CD8 T cell population drives type 1 diabetes
Gearty, S. V., Dündar, F., Zumbo, P., Espinosa-Carrasco, G., Shakiba, M., Sanchez-Rivera, F. J., Socci, N. D., Trivedi, P., Lowe, S. W., Lauer, P., et al. (2022) · Nature · doi:10.1038/s41586-021-04248-x · Cited by 257 · see citing works
Keller, J., Catala-Lehnen, P., Huebner, A. K., Jeschke, A., Heckt, T., Lueth, A., Krause, M., Koehne, T., Albers, J., Schulze, J., et al. (2014) · Nature Communications · doi:10.1038/ncomms6215 · Cited by 211 · see citing works
Sarcopenic obesity: Emerging mechanisms and therapeutic potential
Axelrod, C. L., Dantas, W. S., & Kirwan, J. P. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155639 · Cited by 204 · see citing works
Activation of the <scp>NLRP</scp>3 inflammasome in microglia: the role of ceramide
Scheiblich, H., Schlütter, A., Golenbock, D. T., Latz, E., Martinez‐Martinez, P., & Heneka, M. T. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14225 · Cited by 147 · see citing works
Chun, J., Kihara, Y., Jonnalagadda, D., & Blaho, V. A. (2019) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010818-021358 · Cited by 131 · see citing works
B56δ-related protein phosphatase 2A dysfunction identified in patients with intellectual disability
Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci79860 · Cited by 124 · see citing works
Dusaban, S. S., Chun, J., Rosen, H., Purcell, N. H., & Brown, J. H. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0882-x · Cited by 106 · see citing works
Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease
Xue, R., Su, L., Lai, S., Wang, Y., Zhao, D., Fan, J., Chen, W., Hylemon, P. B., & Zhou, H. (2021) · Cells · doi:10.3390/cells10112806 · Cited by 95 · see citing works
Paroni, M., Maltese, V., De Simone, M., Ranzani, V., Larghi, P., Fenoglio, C., Pietroboni, A. M., De Riz, M. A., Crosti, M. C., Maglie, S., et al. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.11.045 · Cited by 77 · see citing works
Sphingosine 1-phosphate signaling in bone remodeling: multifaceted roles and therapeutic potential
Meshcheryakova, A., Mechtcheriakova, D., & Pietschmann, P. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1332180 · Cited by 74 · see citing works
Colombo, E., Bassani, C., De Angelis, A., Ruffini, F., Ottoboni, L., Comi, G., Martino, G., & Farina, C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00635 · Cited by 66 · see citing works
Kihara, Y., Zhu, Y., Jonnalagadda, D., Romanow, W., Palmer, C., Siddoway, B., Rivera, R., Dutta, R., Trapp, B. D., & Chun, J. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.918041 · Cited by 26 · see citing works
Potential role of regulatory B cells in immunological diseases
Valizadeh, A., Sanaei, R., Rezaei, N., Azizi, G., Fekrvand, S., Aghamohammadi, A., & Yazdani, R. (2019) · Immunology Letters · doi:10.1016/j.imlet.2019.08.004 · Cited by 16 · see citing works
- Authors
- Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., & Burtin, P.
- Affiliations
- Novartis Institutes for BioMedical Research (CH)
- Sandoz Group AG (Switzerland) (CH)
- Novartis (Switzerland) (CH)
- Corresponding author
- Brinkmann, Volker
- Venue
- Nature Reviews Drug Discovery
- Published
- 2010-10-29
- Volume
- 9
- Issue
- 11
- Pages
- 883-897
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W2167876561
- Cited by
- 1,273
- References
- 10
- Citations by year
- 2026: 53 · 2025: 55 · 2024: 58 · 2023: 76 · 2022: 84 · 2021: 71 · 2020: 79 · 2019: 81 · 2018: 78 · 2017: 98 · 2016: 94 · 2015: 99 · 2014: 97 · 2013: 90 · 2012: 76
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Update notices
- erratum (2010-12-01)
- Open access
- closed
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- fingolimod, relapsing-remitting multiple sclerosis, sphingosine-1-phosphate receptor, disease-modifying therapy, lymphocyte migration, astrocytes, drug discovery, drug development, neuroinflammation
- MeSH terms
- Fingolimod Hydrochloride, Administration, Oral, Animals, Humans, Multiple Sclerosis, Propylene Glycols, Research, Sphingosine, Inflammation Mediators, Multiple Sclerosis, Relapsing-Remitting, Drug Discovery
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
