Evidence map›Paper›PMID 40451905›Full record

ArticleDiscover oncology2025

CB5712809, a novel Keap1 inhibitor upregulates SQSTM1/p62 mediated Nrf2 activation to induce cell death in colon cancer cells.

Ayed A Dera, Majed Al Fayi

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Discover oncology, 2025. 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
–field-weighted citation impact
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.

  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

2 authors.

Ayed A DeraDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. ayedd@kku.edu.sa.ORCID http://orcid.org/0000-0002-6248-8983
Majed Al FayiDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.

Funding

Deanship of Scientific Research, King Khalid University RGP2/154/46
6 · The paper itself

Abstract

backgroundThe study focuses on Keap1, a key regulator of the Nrf2 pathway, critical for tumor cell regulation. Recent crystallographic insights into Keap1's structure highlight its functional domains and ligand-binding sites, offering opportunities for targeted drug discovery. The aim is to identify small molecules with high affinity for Keap1 to modulate Keap1, SQSTM1/p62, and Nrf2 functions in colorectal cancer (CRC) cells.

methodsA high-throughput virtual screening approach was used to screen the ChemBridge small library against the Keap1 protein. Atomistic Molecular Dynamics (MD) simulations were conducted using GROMACS, along with Gibbs binding free energy estimations. HCT116 and Caco-2 cells were used to determine anti-proliferation. Flow cytometry was used to evaluate target + inhibition in HCT116 and Caco-2 cells.

resultsThe small molecule CB5712809 demonstrated stable interactions with Keap1, supported by molecular dynamics simulations and MM-PBSA analysis. It suppressed the growth of HCT116 and Caco-2 CRC cells with GI

conclusionResults of this study provide a basis for further experimental validation to develop CB5712809 as a Keap1 targeted chemotherapeutic against CRC.

Indexed as

Cancer therapyComputational approachesDrug discoveryKeap1Molecular dynamics simulationNrf2 pathwayProtein–ligand interactionVirtual screening

Identifiers

PMID40451905
PMCPMC12127251

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Registered trials

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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.