Evidence map›Paper›PMID 40691706›Full record

ArticleScientific reports2025

Potent β-lactam-based tyrosyl-DNA phosphodiesterase 1 inhibitors identified by a virtual screen.

Xue Zhi Zhao, Wenjie Wang, Kiall F Suazo, Md Rasel Al Mahmud, Keli Agama, George T Lountos, Thorkell Andresson, Yves Pommier, Terrence R Burke

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. 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
–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

1 citing paper in PubMed.

  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

9 authors.

Xue Zhi ZhaoChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA. xuezhi.zhao@nih.gov.
Wenjie WangDevelopmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Kiall F SuazoChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Md Rasel Al MahmudDevelopmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Keli AgamaDevelopmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
George T LountosBasic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Thorkell AndressonProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Yves PommierDevelopmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Terrence R BurkeChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
INHIBITORS OF TYROSINE-SPECIFIC PROTEIN KINASES AS ANTICANCER AGENTSZ01BC006198 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BURKE, TERRENCE · 1996 to 2008
$1.6M
PROTEIN-ASSOCIATED DNA BREAKS AS INDICATOR OF TOPOISOMERASE INHIBITIONZ01BC006150 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 1996 to 2008
$1.5M
Intramural NIH HHS Z01 BC006150Intramural NIH HHS Z01 BC006198NCI NIH HHS 75N91019D00024
6 · The paper itself

Abstract

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an important therapeutic target. We recently reported several crystal structures of TDP1 with small molecules bound within the catalytic pocket. These molecules bind by forming hydrogen bonds with residues of the catalytic HKN motifs. Guided by these interactions, in our current work, we used the MolSoft ICM Pro suite of software to perform a virtual screen of the publicly available DrugBank 5.0 (3449 structures) for the ability to bind to the TDP1 catalytic pocket. Among compounds identified as giving good binding scores were several β-lactams. The β-lactam pharmacophore serves as a key component in a range of antibiotics. We subjected a subset of the β-lactam hits to gel-based TDP1 fluorescence catalytic assays and established that certain members showed micromolar TDP1 inhibition. In follow-up, we evaluated a commercially available library of 90 β-lactam antibiotics. This led to our identification of additional β-lactams having micromolar TDP1 inhibitory potencies. In particular, cephalosporin C showed single-digit micromolar TDP1 IC

Indexed as

beta-LactamsPhosphodiesterase InhibitorsPhosphoric Diester HydrolasesCatalytic DomainHumansMolecular Docking SimulationProtein Bindingbeta-LactamsPhosphodiesterase InhibitorsPhosphoric Diester HydrolasesTDP1 protein, humanDrugBankFluorescence assaySurface plasmon resonanceTyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitorsVirtual screenβ-Lactam

Identifiers

PMID40691706
PMCPMC12280126

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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.