Evidence map›Paper›PMID 35948006›Full record

ArticleCell chemical biology2022

Discovery of compounds that reactivate p53 mutants in vitro and in vivo.

Geetha Durairaj, Özlem Demir, Bryant Lim, Roberta Baronio, Delia Tifrea, Linda V Hall, Jacob C DeForest, Linda Lauinger, Maryam M Jebril Fallatah, Clinton Yu and 12 more

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

Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 7% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023
    Pooled it
  2. Article
  3. TowardsbioRxiv : the preprint server for biology · 2025
    Article
  4. Article
  5. Review
  6. Article
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  13. Article
  14. Article
  15. Article
  16. On the linkage of thermodynamics and pathogenicity.Current opinion in structural biology · 2023
    Review
  17. Small-molecule correctors and stabilizers to target p53.Trends in pharmacological sciences · 2023
    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

22 authors at 2 institutions in 1 country.

Geetha DurairajDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92697, USA.
Özlem DemirDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Bryant LimDepartment of Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Roberta BaronioDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Delia TifreaDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Linda V HallDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Jacob C DeForestDepartment of Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Linda LauingerDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Maryam M Jebril FallatahDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Clinton YuDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.
Hosung BaeDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Da-Wei LinDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Jin Kwang KimDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Faezeh SalehiDepartment of Computer Science, University of California, Irvine, Irvine, CA 92697, USA.
Cholsoon JangDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Feng QiaoDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Richard H LathropDepartment of Computer Science, University of California, Irvine, Irvine, CA 92697, USA; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA.
Lan HuangDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.
Robert EdwardsDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Scott RychnovskyDepartment of Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Rommie E AmaroDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: ramaro@ucsd.edu.
Peter KaiserDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: pkaiser@uci.edu.
University of California, Irvine · USUniversity of California, San Diego · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
A Functional Census of p53 Cancer and Suppressor MutantsR01CA112560 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KAISER, PETER, LATHROP, RICHARD H · 2005 to 2013
$3.2M
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
Identification of Small Molecules for Reactivation of p53 Cancer MutantsR21NS063874 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI KAISER, PETER · 2008 to 2008
$146k
NCATS NIH HHS UL1 TR001414NCI NIH HHS P30 CA062203NCI NIH HHS R01 CA112560NCI NIH HHS R21 CA267495NIGMS NIH HHS R01 GM132826NINDS NIH HHS R21 NS063874
6 · The paper itself

Abstract

The tumor suppressor p53 is the most frequently mutated protein in human cancer. The majority of these mutations are missense mutations in the DNA binding domain of p53. Restoring p53 tumor suppressor function could have a major impact on the therapy for a wide range of cancers. Here we report a virtual screening approach that identified several small molecules with p53 reactivation activities. The UCI-LC0023 compound series was studied in detail and was shown to bind p53, induce a conformational change in mutant p53, restore the ability of p53 hotspot mutants to associate with chromatin, reestablish sequence-specific DNA binding of a p53 mutant in a reconstituted in vitro system, induce p53-dependent transcription programs, and prevent progression of tumors carrying mutant p53, but not p53

Indexed as

NeoplasmsTumor Suppressor Protein p53Cell Line, TumorChromatinDNAHumansMutationProtein DomainsChromatinDNATumor Suppressor Protein p53cryptic pocketensemble based virtual screeningmolecular dynamics simulationsmutant p53p53 reactivationsmall molecule p53 corrector drugs

Identifiers

PMID35948006
PMCPMC9481737
OpenAlexW4293865791

What OpenQuestion holds

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LicenceTDM
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 OpenQuestion graph.