ArticleOncotarget2016
The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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.
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.
Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- The role of phosphatidylcholine metabolism in tumors.Medical oncology (Northwood, London, England) · 2025Review
- Hypoxia Dependent Inhibition of Glioblastoma Cell Proliferation, Invasion, and Metabolism by the Choline-Kinase Inhibitor JAS239.Metabolites · 2025Article
- Inhibition of glioblastoma cell proliferation and invasion by the choline-kinase inhibitor JAS239 varies with cell type and hypoxia.bioRxiv : the preprint server for biology · 2024Article
- Is choline kinase alpha a drug target for obesity?Frontiers in endocrinology · 2024Article
- Bench to Bedside Development of [Molecules (Basel, Switzerland) · 2023Review
- Integrative genetic analysis identifies FLVCR1 as a plasma-membrane choline transporter in mammals.Cell metabolism · 2023Article
- Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI).Frontiers in cellular neuroscience · 2023Article
- Bilayer Forming Phospholipids as Targets for Cancer Therapy.International journal of molecular sciences · 2022Review
- Biological Evaluation of New Thienopyridinium and Thienopyrimidinium Derivatives as Human Choline Kinase Inhibitors.Pharmaceutics · 2022Article
- Consideration of Metabolite Efflux in Radiolabelled Choline Kinetics.Pharmaceutics · 2021Article
- Novel Non-Congeneric Derivatives of the Choline Kinase Alpha Inhibitor ICL-CCIC-0019.Pharmaceutics · 2021Article
- DNA Methylation of Human Choline Kinase Alpha Promoter-Associated CpG Islands in MCF-7 Cells.Genes · 2021Article
- Choline Kinase: An Unexpected Journey for a Precision Medicine Strategy in Human Diseases.Pharmaceutics · 2021Review
- The PD-L1 metabolic interactome intersects with choline metabolism and inflammation.Cancer & metabolism · 2021Article
- Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention.Advanced drug delivery reviews · 2020Review
- ChoK-ing the Pathogenic Bacteria: Potential of Human Choline Kinase Inhibitors as Antimicrobial Agents.BioMed research international · 2020Review
- A cell-based high-throughput screen identifies tyrphostin AG 879 as an inhibitor of animal cell phospholipid and fatty acid biosynthesis.Biochemistry and biophysics reports · 2019Article
- Choline Uptake and Metabolism Modulate Macrophage IL-1β and IL-18 Production.Cell metabolism · 2019Article
- Choline kinase inhibitors EB-3D and EB-3P interferes with lipid homeostasis in HepG2 cells.Scientific reports · 2019Article
- 3D Growth of Cancer Cells Elicits Sensitivity to Kinase Inhibitors but Not Lipid Metabolism Modifiers.Molecular cancer therapeutics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis. Changes in phosphocholine cellular levels following treatment could be detected non-invasively in tumor xenografts by [18F]-fluoromethyl-[1,2-2H4]-choline positron emission tomography. Herein, we reveal a previously unappreciated effect of choline metabolism on mitochondria function. Comparative metabolomics demonstrated that phosphatidylcholine pathway inhibition leads to a metabolically stressed phenotype analogous to mitochondria toxin treatment but without reactive oxygen species activation. Drug treatment decreased mitochondria function with associated reduction of citrate synthase expression and AMPK activation. Glucose and acetate uptake were increased in an attempt to overcome the metabolic stress. This study indicates that choline pathway pharmacological inhibition critically affects the metabolic function of the cell beyond reduced synthesis of phospholipids.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.