Evidence map›Paper›PMID 33314657›Full record

ArticleChemMedChem2021

Structure-Based Drug Design of Phenazopyridine Derivatives as Inhibitors of Rev1 Interactions in Translesion Synthesis.

Kerry Silva McPherson, Angela M Zaino, Radha C Dash, Alessandro A Rizzo, Yunfeng Li, Bing Hao, Irina Bezsonova, M Kyle Hadden, Dmitry M Korzhnev

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

Article in ChemMedChem, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Protein-Protein Interactions in Translesion Synthesis.Molecules (Basel, Switzerland) · 2021
    Review
  5. 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

9 authors at 2 institutions in 1 country.

Kerry Silva McPhersonDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA.
Angela M ZainoDepartment of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269, USA.
Radha C DashDepartment of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269, USA.
Alessandro A RizzoDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA.
Yunfeng LiDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA.
Bing HaoDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA.
Irina BezsonovaDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA.
M Kyle HaddenDepartment of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269, USA.ORCID 0000-0001-9482-1712
Dmitry M KorzhnevDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030, USA.ORCID 0000-0002-3556-2447
UConn Health · USUniversity of Connecticut · US

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
UBIQUITIN-PROTEASOME PATHWAY IN CANCERR35GM128864 · NIGMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI BEZSONOVA, IRINA · 2018 to 2022
$1.6M
CT Innovations PITCH2NCI NIH HHS R01 CA233959NCI NIH HHS R01 CA247232NIGMS NIH HHS R35 GM128864
6 · The paper itself

Abstract

Rev1 is a protein scaffold of the translesion synthesis (TLS) pathway, which employs low-fidelity DNA polymerases for replication of damaged DNA. The TLS pathway helps cancers tolerate DNA damage induced by genotoxic chemotherapy, and increases mutagenesis in tumors, thus accelerating the onset of chemoresistance. TLS inhibitors have emerged as potential adjuvant drugs to enhance the efficacy of first-line chemotherapy, with the majority of reported inhibitors targeting protein-protein interactions (PPIs) of the Rev1 C-terminal domain (Rev1-CT). We previously identified phenazopyridine (PAP) as a scaffold to disrupt Rev1-CT PPIs with Rev1-interacting regions (RIRs) of TLS polymerases. To explore the structure-activity relationships for this scaffold, we developed a protocol for co-crystallization of compounds that target the RIR binding site on Rev1-CT with a triple Rev1-CT/Rev7

Indexed as

Drug DesignDose-Response Relationship, DrugEnzyme InhibitorsHumansMolecular StructureNucleotidyltransferasesPhenazopyridineStructure-Activity RelationshipY-Family DNA PolymerasesEnzyme InhibitorsNucleotidyltransferasesPhenazopyridineREV1 protein, humanY-Family DNA Polymerasescancer chemotherapycrystallographyprotein-protein interactionsstructure-activity relationshipstranslesion synthesis inhibitors

Identifiers

PMID33314657
PMCPMC8035318
OpenAlexW3111783845

What OpenQuestion holds

Textmetadata
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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.