Evidence map›Paper›PMID 39740997›Full record

ArticleAngewandte Chemie (International ed. in English)2025

Phenomics-Based Discovery of Novel Orthosteric Choline Kinase Inhibitors.

Ludwig G Bauer, Jennifer A Ward, Laura Díaz-Sáez, Yvonne Sundström, Tuomas Tolvanen, Juan Carlos Alarcón Barrera, Sarantos Kostidis, Catherine M Rogers, Ioanna Panagakou, Usha Singh and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2025. 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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Phenomics-Based Discovery of Novel Orthosteric Choline Kinase Inhibitors.Angewandte Chemie (International ed. in English) · 2025
    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

21 authors.

Ludwig G BauerCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.ORCID 0000-0002-2235-3945
Jennifer A WardCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
Laura Díaz-SáezCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
Yvonne SundströmStructural Genomics Consortium, Karolinska Institutet, 17176, Solna, Sweden.
Tuomas TolvanenStructural Genomics Consortium, Karolinska Institutet, 17176, Solna, Sweden.
Juan Carlos Alarcón BarreraCenter for Proteomics and Metabolomics, Leiden University Medical Center, 2333ZA, Leiden, The Netherlands.
Sarantos KostidisCenter for Proteomics and Metabolomics, Leiden University Medical Center, 2333ZA, Leiden, The Netherlands.
Catherine M RogersCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
Ioanna PanagakouCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
Usha SinghCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
Elisabeth M RothweilerCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
Alejandro Gonzalez OrtaCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
H Ümit KaniskanMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jianping HuMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sonja SieversCompound Management and Screening Center at the Max Planck Institute of Molecular Physiology, 44227, Dortmund, Germany.
Herbert WaldmannDepartment of Chemical Biology, Max Planck Institute of Molecular Physiology, 44227, Dortmund, Germany.ORCID 0000-0002-9606-7247
Martin GieraCenter for Proteomics and Metabolomics, Leiden University Medical Center, 2333ZA, Leiden, The Netherlands.
Michael SundströmStructural Genomics Consortium, Karolinska Institutet, 17176, Solna, Sweden.
Louise BergStructural Genomics Consortium, Karolinska Institutet, 17176, Solna, Sweden.ORCID 0000-0001-6538-2837
Kilian V M HuberCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.ORCID 0000-0002-1103-5300

Funding

Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS) 756/2016H2020 European Research Council 875510
6 · The paper itself

Abstract

Choline kinase alpha (CHKA) is a central mediator of cell metabolism linked to cancer and immune regulation. Cellular and clinical evaluation of CHKA has been hampered by challenges in the development of drug-like choline kinase inhibitors. Here, we identify CHKA as an unexpected off-target of histone methyltransferase inhibitors using an integrated phenomic approach. We confirm CHKA as a direct protein target of the aminoquinazolines UNC0638 and UNC0737 using a combination of chemoproteomic, biochemical, cellular, and metabolic profiling assays, possibly explaining the previously reported discrepancies observed for different G9a/GLP inhibitor scaffolds in cellular assays. Using primary human cell model systems, we discover that CHKA modulation impairs IgG secretion and B-cell maturation consistent with the notion that choline metabolism plays an important role in immune signalling. Co-crystal structures of UNC0638 and UNC0737 with CHKA unravel an unexpected binding mode and suggest the inhibitors as attractive starting points for the development of selective chemical tools to further explore the biological role of CHKA in cancer and immune metabolism.

Indexed as

Choline KinaseDrug DiscoveryEnzyme InhibitorsProtein Kinase InhibitorsQuinazolinesHumansMolecular StructureStructure-Activity RelationshipCHKA protein, humanCholine KinaseEnzyme InhibitorsProtein Kinase InhibitorsQuinazolinescell paintingchemical probeschemical proteomicsmetabolomicsphenotypic

Identifiers

PMID39740997
PMCPMC11811597

What OpenQuestion holds

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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.