Evidence map›Paper›PMID 42619023›Full record

ArticleChemMedChem2026

Docking-Based Virtual Screening Identifies a Small-Molecule Inhibitor of the Translesion Synthesis REV7/REV3 Protein-Protein Interaction.

Noah J Harrahill, Seema M Patel, Radha Charan Dash, Angela M Zaino, Vihit Gupta, Dane H Geddes-Buehre, Colin Brereton, Alessandro A Rizzo, Nimrat Chatterjee, Dmitry M Korzhnev and 1 more

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In one paragraph

Article in ChemMedChem, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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

11 authors.

Noah J HarrahillDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, USA.ORCID https://orcid.org/0000-0002-9958-4717
Seema M PatelDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, USA.
Radha Charan DashDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, USA.ORCID https://orcid.org/0000-0003-0696-4962
Angela M ZainoDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, USA.
Vihit GuptaUniversity of Vermont Cancer Center and Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA.ORCID https://orcid.org/0009-0008-9007-165X
Dane H Geddes-BuehreDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA.ORCID https://orcid.org/0000-0002-1861-0515
Colin BreretonUniversity of Vermont Cancer Center and Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA.ORCID https://orcid.org/0009-0003-6514-0290
Alessandro A RizzoDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA.
Nimrat ChatterjeeUniversity of Vermont Cancer Center and Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA.ORCID https://orcid.org/0000-0001-6556-9423
Dmitry M KorzhnevDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA.ORCID https://orcid.org/0000-0002-3556-2447
M Kyle HaddenDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, USA.ORCID https://orcid.org/0000-0001-9482-1712

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
NCI NIH HHS R01 CA233959NCI NIH HHS R01 CA247232NIH HHS R01 CA2333959NIH HHS R01 CA247232
6 · The paper itself

Abstract

REV7 is an adaptor protein that mediates protein-protein interactions (PPIs) in DNA damage response and cell cycle control. REV7 functions as a subunit of the translesion synthesis (TLS) DNA polymerase POLζ, which is involved in the replicative bypass of DNA lesions. REV7 is also a component of the shieldin complex, which mediates the choice of pathway for DNA double-stranded break (DSB) repair. TLS promotes cancer cell survival after DNA damage and serves as a mechanism through which cancers develop acquired chemoresistance. DSB repair helps cancers mitigate DNA breaks induced by radiation; therefore, inhibition of REV7 PPIs has emerged as a therapeutic strategy. We performed a docking-based virtual screen to identify compounds predicted to disrupt PPIs between REV7 and the REV7-binding motifs (RBMs) found in the REV3 subunit of POLζ (TLS) and the SHLD3 subunit of shieldin (DSB repair). Biochemical analysis of a promising hit compound and several analogues demonstrated the ability of this scaffold to disrupt the REV7/RBM

Indexed as

Antineoplastic AgentsDNA-Binding ProteinsDNA-Directed DNA PolymeraseMad2 ProteinsMolecular Docking SimulationSmall Molecule LibrariesDose-Response Relationship, DrugDrug Evaluation, PreclinicalHumansMolecular StructureProtein BindingStructure-Activity RelationshipTranslesion DNA SynthesisAntineoplastic AgentsDNA-Binding ProteinsDNA-Directed DNA PolymeraseMAD2L2 protein, humanMad2 ProteinsREV3L protein, humanSmall Molecule Librariescancer researchDNA damageDNA polymeraseDNA repairmedicinal chemistrysignal transducing adaptor proteinsmall moleculevirtual screening

Identifiers

PMID42619023
PMCPMC13490628

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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.