Evidence map›Paper›PMID 26990079›Full record

ArticleBritish journal of pharmacology2016

Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity.

F L Scott, B Clemons, J Brooks, E Brahmachary, R Powell, H Dedman, H G Desale, G A Timony, E Martinborough, H Rosen and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 7 pooled it
11.0field-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

168 citing papers in PubMed, 7 syntheses or guidelines pooled it, 299 citations in OpenAlex.

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108 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

13 authors at 2 institutions in 1 country.

F L ScottReceptos Inc, San Diego, CA, USA.
B ClemonsReceptos Inc, San Diego, CA, USA.
J BrooksReceptos Inc, San Diego, CA, USA.
E BrahmacharyReceptos Inc, San Diego, CA, USA.
R PowellReceptos Inc, San Diego, CA, USA.
H DedmanReceptos Inc, San Diego, CA, USA.
H G DesaleReceptos Inc, San Diego, CA, USA.
G A TimonyReceptos Inc, San Diego, CA, USA.
E MartinboroughReceptos Inc, San Diego, CA, USA.
H RosenDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
E RobertsDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
M F BoehmReceptos Inc, San Diego, CA, USA.
R J PeachReceptos Inc, San Diego, CA, USA.
NanoSD (United States) · USScripps Research Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeSphingosine1-phosphate (S1P) receptors mediate multiple events including lymphocyte trafficking, cardiac function, and endothelial barrier integrity. Stimulation of S1P1 receptors sequesters lymphocyte subsets in peripheral lymphoid organs, preventing their trafficking to inflamed tissue sites, modulating immunity. Targeting S1P receptors for treating autoimmune disease has been established in clinical studies with the non-selective S1P modulator, FTY720 (fingolimod, Gilenya™). The purpose of this study was to assess RPC1063 for its therapeutic utility in autoimmune diseases. EXPERIMENTAL APPROACH: The specificity and potency of RPC1063 (ozanimod) was evaluated for all five S1P receptors, and its effect on cell surface S1P1 receptor expression, was characterized in vitro. The oral pharmacokinetic (PK) parameters and pharmacodynamic effects were established in rodents, and its activity in three models of autoimmune disease (experimental autoimmune encephalitis, 2,4,6-trinitrobenzenesulfonic acid colitis and CD4(+) CD45RB(hi) T cell adoptive transfer colitis) was assessed. KEY

resultsRPC1063 was specific for S1P1 and S1P5 receptors, induced S1P1 receptor internalization and induced a reversible reduction in circulating B and CCR7(+) T lymphocytes in vivo. RPC1063 showed high oral bioavailability and volume of distribution, and a circulatory half-life that supports once daily dosing. Oral RPC1063 reduced inflammation and disease parameters in all three autoimmune disease models. CONCLUSIONS AND IMPLICATIONS: S1P receptor selectivity, favourable PK properties and efficacy in three distinct disease models supports the clinical development of RPC1063 for the treatment of relapsing multiple sclerosis and inflammatory bowel disease, differentiates RPC1063 from other S1P receptor agonists, and could result in improved safety outcomes in the clinic.

Indexed as

AnimalsAutoimmune DiseasesDisease Models, AnimalFemaleIndansInflammatory Bowel DiseasesMaleMiceMice, Inbred C57BLMice, SCIDMyelin-Oligodendrocyte GlycoproteinOxadiazolesRatsRats, Sprague-DawleyReceptors, LysosphingolipidTrinitrobenzenesulfonic AcidIndansMog protein, mouseMyelin-Oligodendrocyte GlycoproteinOxadiazolesozanimodReceptors, LysosphingolipidTrinitrobenzenesulfonic Acid

Identifiers

PMID26990079
PMCPMC4867749
OpenAlexW2299774205

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.