Fingolimod: Lessons Learned and New Opportunities for Treating Multiple Sclerosis and Other Disorders
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Fingolimod (FTY720, Gilenya) was the first US Food and Drug Administration–approved oral therapy for relapsing forms of multiple sclerosis (MS). Research on modified fungal metabolites converged with basic science studies that had identified lysophospholipid (LP) sphingosine 1-phosphate (S1P) receptors, providing mechanistic insights on fingolimod while validating LP receptors as drug targets. Mechanism of action (MOA) studies identified receptor-mediated processes involving the immune system and the central nervous system (CNS). These dual actions represent a more general theme for S1P and likely other LP receptor modulators. Fingolimod's direct CNS activities likely contribute to its efficacy in MS, with particular relevance to treating progressive disease stages and forms that involve neurodegeneration. The evolving understanding of fingolimod's MOA has provided strategies for developing next-generation compounds with superior attributes, suggesting new ways to target S1P as well as other LP receptor modulators for novel therapeutics in the CNS and other organ systems.
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Fingolimod and siponimod are approved for multiple sclerosis.
“This strategy has been successfully developed with the S1PR1,3–5 agonist fingolimod167 and the S1PR1,5 agonist siponimod168, which are both approved for the therapy of multiple sclerosis.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [167]
The “Fingolimod (Gilenya) for Multiple Sclerosis” section states that fingolimod received FDA approval for relapsing MS. The “Next-Generation Lysophospholipid Receptor Modulators and Diseases” section describes siponimod as having entered clinical trials and reports positive phase III results, but does not say it was approved. Page numbers are unavailable in our copy. (LLM, conf=0.90)
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- Authors
- Chun, J., Kihara, Y., Jonnalagadda, D., & Blaho, V. A.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Chun, Jerold
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2019-01-06
- Volume
- 59
- Issue
- 1
- Pages
- 149-170
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- PMC
- PMC6392001
- OpenAlex
- W2909092545
- Cited by
- 131
- References
- 165
- Citations by year
- 2026: 19 · 2025: 16 · 2024: 13 · 2023: 18 · 2022: 22 · 2021: 12 · 2020: 18 · 2019: 10 · 2018: 3
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense (#W81XWH-17, W81XWH1710455, W81XWH)
- American Heart Association (16SDG27020014)
- National Institutes of Health (W81XWH, NS103940)
- National Institute of Neurological Disorders and Stroke (R01NS103940, R01NS084398)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- fingolimod, multiple sclerosis, sphingosine-1-phosphate receptor, lysophospholipid receptors, mechanism of action, relapsing multiple sclerosis, neurodegeneration, oral therapy, fungal metabolites, CNS drug targets, drug development
- MeSH terms
- Fingolimod Hydrochloride, Sphingosine-1-Phosphate Receptors, Animals, Central Nervous System, Humans, Lysophospholipids, Multiple Sclerosis
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 ›
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