Evidence map›Paper›PMID 38300970›Full record

ArticleChemMedChem2024

Small Molecule Antagonists of the DNA Repair ERCC1/XPA Protein-Protein Interaction.

Robert Obermann, Bereket Yemane, Cassie Jarvis, Francisco M Franco, Yevhenii Kyriukha, William Nolan, Beth Gohara, Andrzej M Krezel, Scott A Wildman, James W Janetka

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

Article in ChemMedChem, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.7field-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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. 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

10 authors at 1 institution in 1 country.

Robert ObermannWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 S. Euclid Ave., Box 8231, St. Louis, MO, 63110, USA Tel.
Bereket YemaneWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 S. Euclid Ave., Box 8231, St. Louis, MO, 63110, USA Tel.
Cassie JarvisWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 S. Euclid Ave., Box 8231, St. Louis, MO, 63110, USA Tel.
Francisco M FrancoWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 S. Euclid Ave., Box 8231, St. Louis, MO, 63110, USA Tel.
Yevhenii KyriukhaWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 S. Euclid Ave., Box 8231, St. Louis, MO, 63110, USA Tel.
William NolanWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 S. Euclid Ave., Box 8231, St. Louis, MO, 63110, USA Tel.
Beth GoharaWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 S. Euclid Ave., Box 8231, St. Louis, MO, 63110, USA Tel.
Andrzej M KrezelWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 S. Euclid Ave., Box 8231, St. Louis, MO, 63110, USA Tel.
Scott A WildmanWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 S. Euclid Ave., Box 8231, St. Louis, MO, 63110, USA Tel.
James W JanetkaWashington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 S. Euclid Ave., Box 8231, St. Louis, MO, 63110, USA Tel.ORCID 0000-0002-9888-5411
Washington University in St. Louis · US

Funding

STRUCTURAL STUDIES OF DNA REPAIR PROTEINSR01GM052504 · NIGMS · WASHINGTON UNIVERSITY · PI ELLENBERGER, TOM E. · 1995 to 2011
$3.8M
NIGMS NIH HHS R01 GM052504NIH HHS 5R01GM052504
6 · The paper itself

Abstract

The DNA excision repair protein ERCC1 and the DNA damage sensor protein, XPA are highly overexpressed in patient samples of cisplatin-resistant solid tumors including lung, bladder, ovarian, and testicular cancer. The repair of cisplatin-DNA crosslinks is dependent upon nucleotide excision repair (NER) that is modulated by protein-protein binding interactions of ERCC1, the endonuclease, XPF, and XPA. Thus, inhibition of their function is a potential therapeutic strategy for the selective sensitization of tumors to DNA-damaging platinum-based cancer therapy. Here, we report on new small-molecule antagonists of the ERCC1/XPA protein-protein interaction (PPI) discovered using a high-throughput competitive fluorescence polarization binding assay. We discovered a unique structural class of thiopyridine-3-carbonitrile PPI antagonists that block a truncated XPA polypeptide from binding to ERCC1. Preliminary hit-to-lead studies from compound 1 reveal structure-activity relationships (SAR) and identify lead compound 27 o with an EC

Indexed as

CisplatinTesticular NeoplasmsDNADNA-Binding ProteinsDNA DamageDNA RepairEndonucleasesFemaleHumansMalePeptidesXeroderma Pigmentosum Group A ProteinCisplatinDNADNA-Binding ProteinsEndonucleasesERCC1 protein, humanPeptidesXeroderma Pigmentosum Group A ProteinXPA protein, humanDNA damage and repair, cisplatin, chemotherapyERCC1, XPA, XPFhigh-throughput screening (HTS)NMR structurenucleotide excision repair (NER)protein-protein interaction (PPI)small molecule inhibitor

Identifiers

PMID38300970
PMCPMC11031295
OpenAlexW4391428697

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.