Evidence map›Paper›PMID 39199355›Full record

ArticleBiomolecules2024

Pyrimidine Triones as Potential Activators of p53 Mutants.

Maryam M Jebril Fallatah, Özlem Demir, Fiona Law, Linda Lauinger, Roberta Baronio, Linda Hall, Elodie Bournique, Ambuj Srivastava, Landon Tyler Metzen, Zane Norman and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomolecules, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. TowardsbioRxiv : the preprint server for biology · 2025
    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

13 authors.

Maryam M Jebril FallatahDepartment of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.ORCID 0009-0002-1768-3816
Özlem DemirDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Fiona LawDepartment of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.
Linda LauingerDepartment of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.
Roberta BaronioDepartment of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.
Linda HallDepartment of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.
Elodie BourniqueDepartment of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.ORCID 0000-0003-0196-7996
Ambuj SrivastavaDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Landon Tyler MetzenDepartment of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.
Zane NormanDepartment of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.
Rémi BuissonDepartment of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.ORCID 0000-0002-7196-8209
Rommie E AmaroDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Peter KaiserDepartment of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.ORCID 0000-0002-3326-0090

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Molecular Mechanisms of APOBEC-Induced Mutagenesis in CancerR37CA252081 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Remi Buisson · 2021 to 2026
$2.5M
Mechanisms of mutant p53 reactivationR01CA283462 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Peter Kaiser, SCOTT D. RYCHNOVSKY · 2023 to 2026
$2.2M
A MULTISCALE APPROACH TO TARGET THE ACHILLES HEEL OF P53 CANCER MUTANTS (Equipment Supplement)R01GM132826 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AMARO, ROMMIE E · 2019 to 2022
$1.3M
Developing corrector small molecules for reactivation of mutant p53 in cancerR21CA267495 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KAISER, PETER, RYCHNOVSKY, SCOTT D. · 2022 to 2023
$379k
NCI NIH HHS P30 CA062203NCI NIH HHS R01 CA271586-01NCI NIH HHS R01 CA283462NCI NIH HHS R21 CA267495NCI NIH HHS R21 CA267495-01NCI NIH HHS R37 CA252081NCI NIH HHS R37-CA252081NIGMS NIH HHS R01 GM132826NIHGMS 1R01GM132826
6 · The paper itself

Abstract

p53 is a crucial tumor suppressor in vertebrates that is frequently mutated in human cancers. Most mutations are missense mutations that render p53 inactive in suppressing tumor initiation and progression. Developing small-molecule drugs to convert mutant p53 into an active, wild-type-like conformation is a significant focus for personalized cancer therapy. Prior research indicates that reactivating p53 suppresses cancer cell proliferation and tumor growth in animal models. Early clinical evidence with a compound selectively targeting p53 mutants with substitutions of tyrosine 220 suggests potential therapeutic benefits of reactivating p53 in patients. This study identifies and examines the UCI-1001 compound series as a potential corrector for several p53 mutations. The findings indicate that UCI-1001 treatment in p53 mutant cancer cell lines inhibits growth and reinstates wild-type p53 activities, including DNA binding, target gene activation, and induction of cell death. Cellular thermal shift assays, conformation-specific immunofluorescence staining, and differential scanning fluorometry suggest that UCI-1001 interacts with and alters the conformation of mutant p53 in cancer cells. These initial results identify pyrimidine trione derivatives of the UCI-1001 series as candidates for p53 corrector drug development.

Indexed as

PyrimidinesTumor Suppressor Protein p53Antineoplastic AgentsCell Line, TumorCell ProliferationHumansMutationNeoplasmsAntineoplastic AgentsPyrimidinesTP53 protein, humanTumor Suppressor Protein p53cancerCETSADSFmutant p53p53 correctorp53 reactivatortumor suppressor

Identifiers

PMID39199355
PMCPMC11352488

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.