Evidence map›Paper›PMID 38749343›Full record

ArticleBioorganic & medicinal chemistry2024

Lead compound profiling for small molecule inhibitors of the REV1-CT/RIR Translesion synthesis Protein-Protein interaction.

Angela M Zaino, Radha Charan Dash, Stephy J James, Nathan MacGilvary, Andrew Crompton, Kerry S McPherson, Marcello Stanzione, Dmitry M Korzhnev, Nicholas J Dyson, Nimrat Chatterjee and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Sensitization of cancer cells to DNA-damaging agents by expression of the REV1 C-terminal domain: Implications for chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Review
  4. 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

12 authors.

Angela M ZainoDepartment of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Unit 3092, Storrs, CT 06269-3092, USA.
Radha Charan DashDepartment of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Unit 3092, Storrs, CT 06269-3092, USA.
Stephy J JamesDepartment of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Unit 3092, Storrs, CT 06269-3092, USA.
Nathan MacGilvaryMolecular Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Andrew CromptonUniversity of Vermont Cancer Center and Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
Kerry S McPhersonDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT 06030, USA.
Marcello StanzioneMassachusetts General Hospital Cancer Center, 149 13th Street Charlestown, Boston, MA, 02129, USA.
Dmitry M KorzhnevDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT 06030, USA.
Nicholas J DysonMassachusetts General Hospital Cancer Center, 149 13th Street Charlestown, Boston, MA, 02129, USA.
Nimrat ChatterjeeUniversity of Vermont Cancer Center and Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
Sharon B CantorMolecular Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
M Kyle HaddenDepartment of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Unit 3092, Storrs, CT 06269-3092, USA. Electronic address: kyle.hadden@uconn.edu.

Funding

Inhibition of Translesion Synthesis as a Novel Strategy for Cancer ChemotherapyR01CA233959 · NCI · UNIVERSITY OF CONNECTICUT STORRS · PI HADDEN, MATTHEW KYLE, KORZHNEV, DMITRY M. · 2019 to 2023
$2.5M
Targeting replication stress avoidance in cancerR01CA247232 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CANTOR, SHARON B · 2020 to 2024
$2.3M
Mechanistic insights into translesion synthesis-dependent genome instabilityR35GM150992 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Nimrat Chatterjee · 2023 to 2026
$1.5M
NCI NIH HHS R01 CA233959NCI NIH HHS R01 CA247232NIGMS NIH HHS R35 GM150992
6 · The paper itself

Abstract

Translesion synthesis (TLS) is a cellular mechanism through which actively replicating cells recruit specialized, low-fidelity DNA polymerases to damaged DNA to allow for replication past these lesions. REV1 is one of these TLS DNA polymerases that functions primarily as a scaffolding protein to organize the TLS heteroprotein complex and ensure replication occurs in the presence of DNA lesions. The C-Terminal domain of REV1 (REV1-CT) forms many protein-protein interactions (PPIs) with other TLS polymerases, making it essential for TLS function and a promising drug target for anti-cancer drug development. We utilized several lead identification strategies to identify various small molecules capable of disrupting the PPI between REV1-CT and the REV1 Interacting Regions (RIR) present in several other TLS polymerases. These lead compounds were profiled in several in vitro potency and PK assays to identify two scaffolds (1 and 6) as the most promising for further development. Both 1 and 6 synergized with cisplatin in a REV1-dependent fashion and demonstrated promising in vivo PK and toxicity profiles.

Indexed as

NucleotidyltransferasesSmall Molecule LibrariesAnimalsAntineoplastic AgentsDNA-Directed DNA PolymeraseDose-Response Relationship, DrugHumansMiceMolecular StructureProtein BindingStructure-Activity RelationshipTranslesion DNA SynthesisY-Family DNA PolymerasesAntineoplastic AgentsDNA-Directed DNA PolymeraseNucleotidyltransferasesREV1 protein, humanSmall Molecule LibrariesY-Family DNA PolymerasesMedicinal ChemistryREV1 pharmacokineticsSmall moleculesTranslesion synthesis

Identifiers

PMID38749343
PMCPMC11472982

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.