The DOI matches its Crossref record; 165 of the 165 references it cites were found in a registry or an index.
Fingolimod: Lessons Learned and New Opportunities for Treating Multiple Sclerosis and Other Disorders
Open accessAbstract
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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“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]
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Cites
4 retracted
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Cited by
Sorted by citations
Atopic dermatitis: an expanding therapeutic pipeline for a complex disease
Bieber, T. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00266-6 · Cited by 623
Chun, J. J. M., Giovannoni, G., & Hunter, S. F. (2020) · Drugs · doi:10.1007/s40265-020-01431-8 · Cited by 165
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Finding a way out: S1P signaling and immune cell migration
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Metadata
- 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
- 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 › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Genetics (clinical) › 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
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