Evidence map›Paper›PMID 30043096›Full record

ArticleBreast cancer research and treatment2018

Field template-based design and biological evaluation of new sphingosine kinase 1 inhibitors.

Heba Alshaker, Shyam Srivats, Danielle Monteil, Qi Wang, Caroline M R Low, Dmitri Pchejetski

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

Article in Breast cancer research and treatment, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Targeting Sphingosine-1-Phosphate Signaling in Breast Cancer.International journal of molecular sciences · 2024
    Review
  2. Review
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  4. Article
  5. Emerging Roles of Ceramides in Breast Cancer Biology and Therapy.International journal of molecular sciences · 2022
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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

6 authors at 2 institutions in 2 countries.

Heba AlshakerSchool of Medicine, University of East Anglia, 2.53 BCRE, Norwich Research Park, Norwich, NR47UQ, UK. h.alshaker@uea.ac.uk.
Shyam SrivatsDepartment of Surgery and Cancer, Imperial College London, London, UK.
Danielle MonteilDepartment of Surgery and Cancer, Imperial College London, London, UK.
Qi WangSchool of Medicine, University of East Anglia, 2.53 BCRE, Norwich Research Park, Norwich, NR47UQ, UK.
Caroline M R LowDrug Design Consultant, London, UK.
Dmitri PchejetskiSchool of Medicine, University of East Anglia, 2.53 BCRE, Norwich Research Park, Norwich, NR47UQ, UK. d.pshezhetskiy@uea.ac.uk.ORCID http://orcid.org/0000-0003-1074-9261
University of East Anglia · GBImperial College London · GB

Funding

Prostate Cancer UK 12-14University of Petra 01-16
6 · The paper itself

Abstract

purposeSphingosine kinase 1 (SK1) is a protooncogenic enzyme expressed in many human tumours and is associated with chemoresistance and poor prognosis. It is a potent therapy target and its inhibition chemosensitises solid tumours. Despite recent advances in SK1 inhibitors synthesis and validation, their clinical safety and chemosensitising options are not well described. In this study, we have designed, synthesised and tested a new specific SK1 inhibitor with a low toxicity profile.

methodsField template molecular modelling was used for compound design. Lead compounds were tested in cell and mouse cancer models.

resultsField template analysis of three known SK1 inhibitors, SKI-178, 12aa and SK1-I, was performed and compound screening identified six potential new SK1 inhibitors. SK1 activity assays in both cell-free and in vitro settings showed that two compounds were effective SK1 inhibitors. Compound SK-F has potently decreased cancer cell viability in vitro and sensitised mouse breast tumours to docetaxel (DTX) in vivo, without significant whole-body toxicity.

conclusionThrough field template screening, we have identified a new SK1 inhibitor, SK-F, which demonstrated antitumour activity in vitro and in vivo without overt toxicity when combined with DTX.

Indexed as

Amino AlcoholsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCell-Free SystemCell Line, TumorCell SurvivalDocetaxelDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansHydrazinesLigandsMiceModels, MolecularAmino AlcoholsDocetaxelEnzyme InhibitorsHydrazinesLigandsN'-((1E)-1-(3,4-dimethoxyphenyl)ethylidene)-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazideN-methyl-5-(4'-pentylphenyl)-2-aminopent-4-ene-1,3-diolPhosphotransferases (Alcohol Group Acceptor)PyrazolesSphingosine KinaseBreast cancerChemosensitisationDocetaxelKinase inhibitorMolecular field templateSphingosine kinase 1

Identifiers

PMID30043096
PMCPMC6208908
OpenAlexW2883527677

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.