Evidence map›Paper›PMID 35805142›Full record

ReviewCells2022

Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway Modulators, from Current Insights to Future Perspectives.

Gary Álvarez Bravo, René Robles Cedeño, Marc Puig Casadevall, Lluís Ramió-Torrentà

Open access · goldAbstract readReview
In one paragraph

Review in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 4 pooled it
9.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 4 syntheses or guidelines pooled it, 122 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Review
  7. Sphingolipids and Atherosclerosis.Current atherosclerosis reports · 2026
    Review
  8. Article
  9. Article
  10. Observational
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Rethinking MS Therapeutics: From Disease Pathogenesis Mechanisms to AI-Driven Drug Discovery.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Review
  18. Article
  19. Article
  20. Article

28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Gary Álvarez BravoGirona Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Dr. Josep Trueta University Hospital, Girona Biomedical Research Institute (IDIBGI), 17007 Girona, Spain.
René Robles CedeñoGirona Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Dr. Josep Trueta University Hospital, Girona Biomedical Research Institute (IDIBGI), 17007 Girona, Spain.
Marc Puig CasadevallGirona Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Dr. Josep Trueta University Hospital, Girona Biomedical Research Institute (IDIBGI), 17007 Girona, Spain.
Lluís Ramió-TorrentàGirona Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Dr. Josep Trueta University Hospital, Girona Biomedical Research Institute (IDIBGI), 17007 Girona, Spain.ORCID 0000-0002-6999-1004
Institut d'Investigació Biomèdica de Girona · ESUniversitat de Girona · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are bioactive lipid molecules that are ubiquitously expressed in the human body and play an important role in the immune system. S1P-S1PR signaling has been well characterized in immune trafficking and activation in both innate and adaptive immune systems. Despite this knowledge, the full scope in the pathogenesis of autoimmune disorders is not well characterized yet. From the discovery of fingolimod, the first S1P modulator, until siponimod, the new molecule recently approved for the treatment of secondary progressive multiple sclerosis (SPMS), there has been a great advance in understanding the S1P functions and their involvement in immune diseases, including multiple sclerosis (MS). Modulation on S1P is an interesting target for the treatment of various autoimmune disorders. Improved understanding of the mechanism of action of fingolimod has allowed the development of the more selective second-generation S1PR modulators. Subtype 1 of the S1PR (S1PR1) is expressed on the cell surface of lymphocytes, which are known to play a major role in MS pathogenesis. The understanding of S1PR1's role facilitated the development of pharmacological strategies directed to this target, and theoretically reduced the safety concerns derived from the use of fingolimod. A great advance in the MS treatment was achieved in March 2019 when the Food and Drug Association (FDA) approved Siponimod, for both active secondary progressive MS and relapsing-remitting MS. Siponimod became the first oral disease modifying therapy (DMT) specifically approved for active forms of secondary progressive MS. Additionally, for the treatment of relapsing forms of MS, ozanimod was approved by FDA in March 2020. Currently, there are ongoing trials focused on other new-generation S1PR1 modulators. This review approaches the fundamental aspects of the sphingosine phosphate modulators and their main similarities and differences.

Indexed as

Autoimmune DiseasesMultiple SclerosisFingolimod HydrochlorideHumansLysophospholipidsReceptors, LysosphingolipidSignal TransductionSphingosineFingolimod HydrochlorideLysophospholipidsReceptors, LysosphingolipidSphingosinesphingosine 1-phosphatefingolimodmultiple sclerosisozanimodS1PS1PR1siponimod

Identifiers

PMID35805142
PMCPMC9265592
OpenAlexW4283689652

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.