Evidence map›Paper›PMID 37870431›Full record

ArticleJournal of medicinal chemistry2023

Synthesis and Conformational Analysis of FR901464-Based RNA Splicing Modulators and Their Synergism in Drug-Resistant Cancers.

Jacob P Beard, Robert K Bressin, Paulo L Markaj, John C Schmitz, Kazunori Koide

Open access · hybridAbstract read
In one paragraph

Article in Journal of medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

7 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025
    Review
  5. Article
  6. Review
  7. Article
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

5 authors at 1 institution in 1 country.

Jacob P BeardDepartment of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.ORCID 0000-0002-3428-5345
Robert K BressinDepartment of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.ORCID 0000-0003-4947-1156
Paulo L MarkajDepartment of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.
John C SchmitzDivision of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, 5150 Centre Avenue, Pittsburgh, Pennsylvania 15232, United States.ORCID 0000-0001-6321-9606
Kazunori KoideDepartment of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.ORCID 0000-0001-8894-8485
University of Pittsburgh · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
NCI NIH HHS P30 CA047904
6 · The paper itself

Abstract

FR901464 is a cytotoxic natural product that binds splicing factor 3B subunit 1 (SF3B1) and PHD finger protein 5A (PHF5A), the components of the human spliceosome. The amide-containing tetrahydropyran ring binds SF3B1, and it remains unclear how the substituents on the ring contribute to the binding. Here, we synthesized meayamycin D, an analogue of FR901464, and three additional analogues to probe the conformation through methyl scanning. We discovered that the amide-containing tetrahydropyran ring assumes only one of the two possible chair conformations and that methylation of the nitrogen distorts the chair form, dramatically reducing cytotoxicity. Meayamycin D induced alternative splicing of

Indexed as

NeoplasmsPyransRNA SplicingSpiro CompoundsAmidesAnimalsEpoxy CompoundsHumansMicePhosphoproteinsRNA-Binding ProteinsTrans-ActivatorsAmidesEpoxy CompoundsFR 901464meayamycinmeayamycin DPHF5A protein, humanPhosphoproteinsPyransRNA-Binding ProteinsSpiro CompoundsTrans-Activators

Identifiers

PMID37870431
PMCPMC10641826
OpenAlexW4387865706

What Socratic 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 Socratic graph.