Evidence map›Paper›PMID 25788259›Full record

ArticleOncotarget2015

A selective ATP-competitive sphingosine kinase inhibitor demonstrates anti-cancer properties.

Melissa R Pitman, Jason A Powell, Carl Coolen, Paul A B Moretti, Julia R Zebol, Duyen H Pham, John W Finnie, Anthony S Don, Lisa M Ebert, Claudine S Bonder and 2 more

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

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 74 citations in OpenAlex.

  1. Review
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  4. Targeting Sphingosine-1-Phosphate Signaling in Breast Cancer.International journal of molecular sciences · 2024
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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

12 authors at 6 institutions in 1 country.

Melissa R PitmanCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia.
Jason A PowellCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia.
Carl CoolenCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia.
Paul A B MorettiCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia.
Julia R ZebolCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia.
Duyen H PhamCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia.
John W FinnieSchool of Veterinary Science, University of Adelaide, SA 5005, Australia.
Anthony S DonPrince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
Lisa M EbertCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia.
Claudine S BonderCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia.
Briony L GliddonCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia.
Stuart M PitsonCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia.
University of South Australia · AUSouth Australia Pathology · AUCentre for Cancer Biology · AUHanson Institute · AUUniversity of Adelaide · AUUNSW Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The dynamic balance of cellular sphingolipids, the sphingolipid rheostat, is an important determinant of cell fate, and is commonly deregulated in cancer. Sphingosine 1-phosphate is a signaling molecule with anti-apoptotic, pro-proliferative and pro-angiogenic effects, while conversely, ceramide and sphingosine are pro-apoptotic. The sphingosine kinases (SKs) are key regulators of this sphingolipid rheostat, and are attractive targets for anti-cancer therapy. Here we report a first-in-class ATP-binding site-directed small molecule SK inhibitor, MP-A08, discovered using an approach of structural homology modelling of the ATP-binding site of SK1 and in silico docking with small molecule libraries. MP-A08 is a highly selective ATP competitive SK inhibitor that targets both SK1 and SK2. MP-A08 blocks pro-proliferative signalling pathways, induces mitochondrial-associated apoptosis in a SK-dependent manner, and reduces the growth of human lung adenocarcinoma tumours in a mouse xenograft model by both inducing tumour cell apoptosis and inhibiting tumour angiogenesis. Thus, this selective ATP competitive SK inhibitor provides a promising candidate for potential development as an anti-cancer therapy, and also, due to its different mode of inhibition to other known SK inhibitors, both validates the SKs as targets for anti-cancer therapy, and represents an important experimental tool to study these enzymes.

Indexed as

AdenocarcinomaAdenosine TriphosphateAnimalsAntineoplastic AgentsApoptosisBinding SitesCell LineCell Line, TumorEnzyme InhibitorsFemaleHEK293 CellsHumansLung NeoplasmsMaleMCF-7 CellsMiceAdenosine TriphosphateAntineoplastic AgentsEnzyme InhibitorsPhosphotransferases (Alcohol Group Acceptor)SphingolipidsSphingosine Kinaseapoptosisin silico dockingmolecular modelingsmall molecule inhibitorsphingosine kinase

Identifiers

PMID25788259
PMCPMC4466670
OpenAlexW1543556834

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.