Evidence map›Paper›PMID 36938545›Full record

ArticleMolecular therapy oncolytics2023

A novel chemical attack on Notch-mediated transcription by targeting the NACK ATPase.

Giulia Diluvio, Tanya T Kelley, Mohini Lahiry, Annamil Alvarez-Trotta, Ellen M Kolb, Elena Shersher, Luisana Astudillo, Rhett A Kovall, Stephan C Schürer, Anthony J Capobianco

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

Article in Molecular therapy oncolytics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

10 authors at 4 institutions in 1 country.

Giulia DiluvioMolecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Tanya T KelleySylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Mohini LahiryMolecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Annamil Alvarez-TrottaMolecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Ellen M KolbDepartment of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OH 45267, USA.
Elena ShersherMolecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Luisana AstudilloMolecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Rhett A KovallDepartment of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OH 45267, USA.
Stephan C SchürerSylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Anthony J CapobiancoMolecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Sylvester Comprehensive Cancer Center · USMolecular Oncology (United States) · USUniversity of Cincinnati · USUniversity of Miami · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Notch activation complex kinase (NACK) is a component of the Notch transcriptional machinery critical for the Notch-mediated tumorigenesis. However, the mechanism through which NACK regulates Notch-mediated transcription is not well understood. Here, we demonstrate that NACK binds and hydrolyzes ATP and that only ATP-bound NACK can bind to the Notch ternary complex (NTC). Considering this, we sought to identify inhibitors of this ATP-dependent function and, using computational pipelines, discovered the first small-molecule inhibitor of NACK, Z271-0326, that directly blocks the activity of Notch-mediated transcription and shows potent antineoplastic activity in PDX mouse models. In conclusion, we have discovered the first inhibitor that holds promise for the efficacious treatment of Notch-driven cancers by blocking the Notch activity downstream of the NTC.

Indexed as

ATPaseesophageal adenocarcinomaNotch inhibitionNotch signalingpseudokinaseSGK223small-molecule inhibitor

Identifiers

PMID36938545
PMCPMC10015116
OpenAlexW4321502861

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.