Evidence map›Paper›PMID 35877475›Full record

ArticleMolecular cancer therapeutics2022

Decreased DNA Damage and Improved p53 Specificity of RITA Analogs.

Yue Zhan, Xiaolei Zhou, Sylvain Peuget, Madhurendra Singh, Brian D Peyser, Zhimin Fan, Galina Selivanova

Open access · hybridAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2022. 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
0.5field-weighted citation impact, top 33% 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, 5 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

7 authors at 3 institutions in 5 countries.

Yue ZhanDepartment of Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-2514-249X
Xiaolei ZhouDepartment of Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-7293-4641
Sylvain PeugetDepartment of Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-3315-1935
Madhurendra SinghDepartment of Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-9935-5706
Brian D PeyserDivision of Cancer Treatment and Diagnosis, Developmental Therapeutics Program, National Cancer Institute, Bethesda, Maryland.ORCID 0000-0002-3455-5181
Zhimin FanDepartment of Breast Surgery, The First Hospital of Jilin University, Changchun, China.ORCID 0000-0003-1996-6414
Galina SelivanovaDepartment of Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-8698-4332
Karolinska Institutet · SEJilin University · CNNational Cancer Institute · UA

Funding

Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

Reactivation of p53 tumor-suppressor function by small molecules is an attractive strategy to defeat cancer. A potent p53-reactivating molecule RITA, which triggers p53-dependent apoptosis in human tumor cells in vitro and in vivo, exhibits p53-independent cytotoxicity due to modifications by detoxification enzyme Sulfotransferase 1A1 (SULT1A1), producing a reactive carbocation. Several synthetic modifications to RITA's heterocyclic scaffold lead to higher energy barriers for carbocation formation. In this study, we addressed the question whether RITA analogs NSC777196 and NSC782846 can induce p53-dependent apoptosis without SULT1A1-dependent DNA damage. We found that RITA analog NSC782846, but not NSC777196, induced p53-regulated genes, targeted oncogene addiction, and killed cancer cells upon p53 reactivation, but without induction of DNA damage and inhibition RNA pol II. Our results might demonstrate a method for designing more specific and potent RITA analogs to accelerate translation of p53-targeting compounds from laboratory bench to clinic.

Indexed as

RNA Polymerase IITumor Suppressor Protein p53ApoptosisCell Line, TumorDNA DamageFuransHumansSulfotransferasesFuransRNA Polymerase IISulfotransferasesTumor Suppressor Protein p53

Identifiers

PMID35877475
PMCPMC9538593
OpenAlexW4287510124

What OpenQuestion holds

Textmetadata
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.