Evidence map›Paper›PMID 38609948›Full record

ArticleBMC biology2024

Targeting of REST with rationally-designed small molecule compounds exhibits synergetic therapeutic potential in human glioblastoma cells.

Svetlana B Panina, Joshua V Schweer, Qian Zhang, Gaurav Raina, Haley A Hardtke, Seungjin Kim, Wanjie Yang, Dionicio Siegel, Y Jessie Zhang

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

Article in BMC biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. 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

9 authors at 2 institutions in 1 country.

Svetlana B PaninaDepartment of Molecular Biosciences, The University of Texas at Austin, 2500 Speedway, Austin, TX, USA.
Joshua V SchweerSkaggs School of Pharmacy and Pharmaceutical Sciences, The University of California San Diego, 9500 Gilman Drive 0741, La Jolla, CA, USA.
Qian ZhangDepartment of Molecular Biosciences, The University of Texas at Austin, 2500 Speedway, Austin, TX, USA.
Gaurav RainaSkaggs School of Pharmacy and Pharmaceutical Sciences, The University of California San Diego, 9500 Gilman Drive 0741, La Jolla, CA, USA.
Haley A HardtkeDepartment of Molecular Biosciences, The University of Texas at Austin, 2500 Speedway, Austin, TX, USA.
Seungjin KimDepartment of Molecular Biosciences, The University of Texas at Austin, 2500 Speedway, Austin, TX, USA.
Wanjie YangDepartment of Molecular Biosciences, The University of Texas at Austin, 2500 Speedway, Austin, TX, USA.
Dionicio SiegelSkaggs School of Pharmacy and Pharmaceutical Sciences, The University of California San Diego, 9500 Gilman Drive 0741, La Jolla, CA, USA.
Y Jessie ZhangDepartment of Molecular Biosciences, The University of Texas at Austin, 2500 Speedway, Austin, TX, USA. jzhang@cm.utexas.edu.ORCID http://orcid.org/0000-0002-9360-5388
The University of Texas at Austin · USUniversity of California San Diego · US

Funding

Gene-specific transcriptional silencing directed by dephosphorylation of RNAP IIR01GM104896 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI ZHANG, YAN JESSIE · 2013 to 2022
$2.4M
Deciphering the phosphorylation pattern of RNA polymerase II for eukaryotic transcriptionR35GM148356 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI Yan Jessie Zhang · 2023 to 2026
$2.3M
Interpretation of the phosphorylation code of RNA polymerase II during eukaryotic transcriptionR01GM125882 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI BRODBELT, JENNIFER S., ZHANG, YAN JESSIE · 2018 to 2021
$1.4M
NIGMS NIH HHS R01 GM104896NIGMS NIH HHS R01GM104896NIGMS NIH HHS R01 GM125882NIGMS NIH HHS R35 GM148356NIGMS NIH HHS R35GM148356
6 · The paper itself

Abstract

backgroundGlioblastoma (GBM) is an aggressive brain cancer associated with poor prognosis, intrinsic heterogeneity, plasticity, and therapy resistance. In some GBMs, cell proliferation is fueled by a transcriptional regulator, repressor element-1 silencing transcription factor (REST).

resultsUsing CRISPR/Cas9, we identified GBM cell lines dependent on REST activity. We developed new small molecule inhibitory compounds targeting small C-terminal domain phosphatase 1 (SCP1) to reduce REST protein level and transcriptional activity in glioblastoma cells. Top leads of the series like GR-28 exhibit potent cytotoxicity, reduce REST protein level, and suppress its transcriptional activity. Upon the loss of REST protein, GBM cells can potentially compensate by rewiring fatty acid metabolism, enabling continued proliferation. Combining REST inhibition with the blockade of this compensatory adaptation using long-chain acyl-CoA synthetase inhibitor Triacsin C demonstrated substantial synergetic potential without inducing hepatotoxicity.

conclusionsOur results highlight the efficacy and selectivity of targeting REST alone or in combination as a therapeutic strategy to combat high-REST GBM.

Indexed as

GlioblastomaTranscription FactorsBrainGene Expression RegulationHumansTranscription FactorsGlioblastoma (GBM)Repressor element-1 silencing transcription factorSCP1 phosphataseSynergy

Identifiers

PMID38609948
PMCPMC11015551
OpenAlexW4394769065

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.