Evidence map›Paper›PMID 30143424›Full record

ArticleBioorganic & medicinal chemistry letters2018

Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1.

Mark Bell, David Foley, Claire Naylor, Colin Robinson, Jennifer Riley, Ola Epemolu, Paul Scullion, Yoko Shishikura, Elad Katz, W H Irwin McLean and 3 more

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

Article in Bioorganic & medicinal chemistry letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Soft drugs: design principles and topical applications.Nature reviews. Drug discovery · 2026
    Review
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  3. Article
  4. Review
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  6. Article
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  12. New Treatment Addressing the Pathogenesis of Psoriasis.International journal of molecular sciences · 2020
    Review
  13. Article
  14. Article
  15. Review
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 1 institution in 1 country.

Mark BellThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK. Electronic address: m.u.bell@dundee.ac.uk.
David FoleyThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
Claire NaylorThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
Colin RobinsonThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
Jennifer RileyThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
Ola EpemoluThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
Paul ScullionThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
Yoko ShishikuraThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
Elad KatzThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
W H Irwin McLeanDermatology and Genetic Medicine, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK.
Paul WyattThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
Kevin D ReadThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK.
Andrew WoodlandThe Drug Discovery Unit, Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 4HN, UK. Electronic address: awoodland@dundee.ac.uk.
University of Dundee · GB

Funding

Wellcome TrustWellcome Trust 098439/Z/12/Z
6 · The paper itself

Abstract

The oral S1PR1 agonist ponesimod demonstrated substantial efficacy in a phase II clinical trial of psoriasis. Unfortunately, systemic side effects were observed, which included lymphopenia and transient bradycardia. We sought to develop a topical soft-drug S1PR1 agonist with an improved therapeutic index. By modifying ponesimod, we discovered an ester series of S1PR agonists. To increase metabolic instability in plasma we synthesised esters described as specific substrates for paraoxonase and butyrylcholinesterases, esterases present in human plasma.

Indexed as

Drug DiscoveryAdministration, TopicalAryldialkylphosphataseChromatography, High Pressure LiquidChromatography, Reverse-PhaseEsterasesHumansReceptors, LysosphingolipidSkinSolubilitySphingosine-1-Phosphate ReceptorsStructure-Activity RelationshipThiazolesAryldialkylphosphataseEsterasesponesimodReceptors, LysosphingolipidS1PR1 protein, humanSphingosine-1-Phosphate ReceptorsThiazolesPlasma stabilityPsoriasisS1PR1Soft-drugTopical

Identifiers

PMID30143424
PMCPMC6185871
OpenAlexW2887008418

What OpenQuestion 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 OpenQuestion graph.