Article in Chemical science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
0numbers the graph read from it
0cells of the map it votes in
2citing 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.
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
19 authors.
Marcin BielinskiChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford Mansfield Road Oxford OX1 3TA UK christopher.schofield@chem.ox.ac.uk.ORCID https://orcid.org/0000-0002-3580-6106
Lucy R HendersonDepartment of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital Oxford OX3 9DS UK peter.mchugh@imm.ox.ac.uk.ORCID https://orcid.org/0000-0002-0142-5444
Yuliana YosaatmadjaCentre for Medicines Discovery, NDM Research Building, University of Oxford Old Road Campus Research Building, Roosevelt Drive Oxford OX3 7DQ UK joseph.newman@cmd.ox.ac.uk.
Lonnie P SwiftDepartment of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital Oxford OX3 9DS UK peter.mchugh@imm.ox.ac.uk.
Hannah T BaddockDepartment of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital Oxford OX3 9DS UK peter.mchugh@imm.ox.ac.uk.
Matthew J BowenChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford Mansfield Road Oxford OX1 3TA UK christopher.schofield@chem.ox.ac.uk.ORCID https://orcid.org/0000-0002-4396-7874
Jürgen BremChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford Mansfield Road Oxford OX1 3TA UK christopher.schofield@chem.ox.ac.uk.ORCID https://orcid.org/0000-0002-0137-3226
Philip S JonesUniversity of Dundee, European Screening Centre Newhouse ML1 5UH UK.
Stuart P McElroyUniversity of Dundee, European Screening Centre Newhouse ML1 5UH UK.
Angus MorrisonUniversity of Dundee, European Screening Centre Newhouse ML1 5UH UK.
Stan van BoeckelPivot Park Screening Centre 5349 AB Oss The Netherlands.
Els van DoornmalenPivot Park Screening Centre 5349 AB Oss The Netherlands.
Jan van GroningenPivot Park Screening Centre 5349 AB Oss The Netherlands.
Helma van den HurkPivot Park Screening Centre 5349 AB Oss The Netherlands.
Opher GileadiCentre for Medicines Discovery, NDM Research Building, University of Oxford Old Road Campus Research Building, Roosevelt Drive Oxford OX3 7DQ UK joseph.newman@cmd.ox.ac.uk.ORCID https://orcid.org/0000-0001-6886-898X
Joseph A NewmanCentre for Medicines Discovery, NDM Research Building, University of Oxford Old Road Campus Research Building, Roosevelt Drive Oxford OX3 7DQ UK joseph.newman@cmd.ox.ac.uk.
Peter J McHughDepartment of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital Oxford OX3 9DS UK peter.mchugh@imm.ox.ac.uk.ORCID https://orcid.org/0000-0002-8679-4627
Christopher J SchofieldChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford Mansfield Road Oxford OX1 3TA UK christopher.schofield@chem.ox.ac.uk.ORCID https://orcid.org/0000-0002-0290-6565
Funding
Wellcome Trust
6 · The paper itself
Abstract
The three human SNM1 metallo-β-lactamase fold nucleases (SNM1A-C) play key roles in DNA damage repair and in maintaining telomere integrity. Genetic studies indicate that they are attractive targets for cancer treatment and to potentiate chemo- and radiation-therapy. A high-throughput screen for SNM1A inhibitors identified diverse pharmacophores, some of which were shown by crystallography to coordinate to the di-metal ion centre at the SNM1A active site. Structure and turnover assay-guided optimization enabled the identification of potent quinazoline-hydroxamic acid containing inhibitors, which bind in a manner where the hydroxamic acid displaces the hydrolytic water and the quinazoline ring occupies a substrate nucleobase binding site. Cellular assays reveal that SNM1A inhibitors cause sensitisation to, and defects in the resolution of, cisplatin-induced DNA damage, validating the tractability of MBL fold nucleases as cancer drug targets.
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.
Cell-active small molecule inhibitors validate the SNM1A DNA repair nuclease as a cancer target. · full record | OpenQuestion