Evidence map›Paper›PMID 32567455›Full record

ArticleSLAS discovery : advancing life sciences R & D2020

A Novel Flow Cytometric Assay to Identify Inhibitors of RBPJ-DNA Interactions.

Robert J Lake, Mark K Haynes, Kostiantyn Dreval, Rabeya Bilkis, Larry A Sklar, Hua-Ying Fan

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

Article in SLAS discovery : advancing life sciences R & D, 2020. 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
0.2field-weighted citation impact, top 50% 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, 4 citations in OpenAlex.

  1. Article
  2. 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

6 authors at 3 institutions in 1 country.

Robert J LakeDepartment of Internal Medicine, Division of Molecular Medicine, Program in Cellular and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
Mark K HaynesDepartment of Pathology, Program in Cancer Therapeutics, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
Kostiantyn DrevalDepartment of Internal Medicine, Division of Molecular Medicine, Program in Cellular and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
Rabeya BilkisDepartment of Internal Medicine, Division of Molecular Medicine, Program in Cellular and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
Larry A SklarDepartment of Pathology, Program in Cancer Therapeutics, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
Hua-Ying FanDepartment of Internal Medicine, Division of Molecular Medicine, Program in Cellular and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
University of New Mexico · USNew Mexico Cancer Center · USUNM Comprehensive Cancer Center

Funding

WOMEN'S CANCERS RESEARCH PROGRAMP30CA118100 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Yolanda Sanchez · 2005 to 2026
$57.1M
NCI NIH HHS P30 CA118100
6 · The paper itself

Abstract

Notch signaling is often involved in cancer cell initiation and proliferation. Aberrant Notch activation underlies more than 50% of T-cell acute lymphoblastic leukemia (T-ALL); accordingly, chemicals disrupting Notch signaling are of potential to treat Notch-dependent cancer. Here, we developed a flow cytometry-based high-throughput assay to identify compounds that disrupt the interactions of DNA and RBPJ, the major downstream effector of Notch signaling. From 1492 compounds, we identified 18 compounds that disrupt RBPJ-DNA interactions in a dose-dependent manner. Cell-based assays further revealed that auranofin downregulates Notch-dependent transcription and decreases RBPJ-chromatin interactions in cells. Most strikingly, T-ALL cells that depend on Notch signaling for proliferation are more sensitive to auranofin treatment, supporting the notion that auranofin downregulates Notch signaling by disrupting RBPJ-DNA interaction. These results validate the feasibility of our assay scheme to screen for additional Notch inhibitors and provide a rationale to further test the use of auranofin in treating Notch-dependent cancer.

Indexed as

AuranofinCell Line, TumorCell ProliferationDNADNA-Binding ProteinsFlow CytometryHigh-Throughput Screening AssaysHumansImmunoglobulin J Recombination Signal Sequence-Binding ProteinPrecursor T-Cell Lymphoblastic Leukemia-LymphomaReceptors, NotchSignal TransductionAuranofinDNADNA-Binding ProteinsImmunoglobulin J Recombination Signal Sequence-Binding ProteinRBPJ protein, humanReceptors, Notchauranofinflow cytometry-based high-throughput screeningNotch inhibitorRBPJ-DNA interactionsT-ALL

Identifiers

PMID32567455
PMCPMC7442708
OpenAlexW3036784541

What OpenQuestion holds

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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.