Evidence map›Paper›PMID 18826947›Full record

ArticleThe Journal of biological chemistry2008

The biflavonoid isoginkgetin is a general inhibitor of Pre-mRNA splicing.

Kristine O'Brien, Arianne J Matlin, April M Lowell, Melissa J Moore

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

125 citing papers in PubMed, 199 citations in OpenAlex.

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  13. Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025
    Review
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65 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 3 institutions in 1 country.

Kristine O'BrienHoward Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA.
Arianne J Matlin
April M Lowell
Melissa J Moore
Howard Hughes Medical Institute · USBrandeis University · USUniversity of Massachusetts Chan Medical School · US

Funding

GENETIC AND BIOCHEMICAL MECHANISMS OF REGULATIONT32GM007122 · NIGMS · BRANDEIS UNIVERSITY · PI LOVETT, SUSAN THOMAS · 1985 to 2020
$7.5M
Howard Hughes Medical InstituteNCI NIH HHS N01-CO-12400NIGMS NIH HHS R01-GM35007NIGMS NIH HHS T32 GM007122
6 · The paper itself

Abstract

Membrane-permeable compounds that reversibly inhibit a particular step in gene expression are highly useful tools for cell biological and biochemical/structural studies. In comparison with other gene expression steps where multiple small molecule effectors are available, very few compounds have been described that act as general inhibitors of pre-mRNA splicing. Here we report construction and validation of a set of mammalian cell lines suitable for the identification of small molecule inhibitors of pre-mRNA splicing. Using these cell lines, we identified the natural product isoginkgetin as a general inhibitor of both the major and minor spliceosomes. Isoginkgetin inhibits splicing both in vivo and in vitro at similar micromolar concentrations. It appears to do so by preventing stable recruitment of the U4/U5/U6 tri-small nuclear ribonucleoprotein, resulting in accumulation of the prespliceosomal A complex. Like two other recently reported general pre-mRNA splicing inhibitors, isoginkgetin has been previously described as an anti-tumor agent. Our results suggest that splicing inhibition is the mechanistic basis of the anti-tumor activity of isoginkgetin. Thus, pre-mRNA splicing inhibitors may represent a novel avenue for development of new anti-cancer agents.

Indexed as

Antineoplastic AgentsBiflavonoidsCell LineDose-Response Relationship, DrugHumansRibonucleoprotein, U4-U6 Small NuclearRibonucleoprotein, U5 Small NuclearRNA PrecursorsRNA SplicingSpliceosomesAntineoplastic AgentsBiflavonoidsisoginkgetinRibonucleoprotein, U4-U6 Small NuclearRibonucleoprotein, U5 Small NuclearRNA Precursors

Identifiers

PMID18826947
PMCPMC2586251
OpenAlexW2055104884

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.