ArticleInternational journal of molecular sciences2019
Evaluation of Protein Kinase Inhibitors with PLK4 Cross-Over Potential in a Pre-Clinical Model of Cancer.
Article in International journal of molecular sciences, 2019. 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, 46 citations in OpenAlex.
- Design, Synthesis, and Biological Activity Evaluation of Quinazoline-Based PLK4 Inhibitors.Biomedicines · 2026Article
- Expanding Therapeutic Horizons with Indazole-Based Compounds: A Review of Anticancer, Antimicrobial, and Neuroprotective Applications.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2026Review
- PLK4: Master Regulator of Centriole Duplication and Its Therapeutic Potential.Cytoskeleton (Hoboken, N.J.) · 2025Review
- PLK4 as a potential target to enhance radiosensitivity in triple-negative breast cancer.Radiation oncology (London, England) · 2024Article
- Seize the engine: Emerging cell cycle targets in breast cancer.Clinical and translational medicine · 2024Review
- Design, synthesis, and biological evaluation of novel pyrimidin-2-amine derivatives as potent PLK4 inhibitors.RSC medicinal chemistry · 2023Article
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Polo-like kinase 4 (Plk4) potentiates anoikis-resistance of p53KO mammary epithelial cells by inducing a hybrid EMT phenotype.Cell death & disease · 2023Article
- TFEB- and TFE3-dependent autophagy activation supports cancer proliferation in the absence of centrosomes.Autophagy · 2022Article
- Centrosome Defects in Hematological Malignancies: Molecular Mechanisms and Therapeutic Insights.Blood science (Baltimore, Md.) · 2022Review
- Downregulation of PLK4 expression induces apoptosis and G0/G1-phase cell cycle arrest in keloid fibroblasts.Cell proliferation · 2022Article
- Global cellular response to chemical perturbation of PLK4 activity and abnormal centrosome number.eLife · 2022Article
- Current and Emerging Therapeutic Approaches for Extracranial Malignant Rhabdoid Tumors.Cancer management and research · 2022Review
- Antiangiogenic Compound Axitinib Demonstrates Low Toxicity and Antitumoral Effects against Medulloblastoma.Cancers · 2021Article
- Synthetic Strategies of Pyrimidine-Based Scaffolds as Aurora Kinase and Polo-like Kinase Inhibitors.Molecules (Basel, Switzerland) · 2021Review
- Review
- Polo-Like Kinase 4's Critical Role in Cancer Development and Strategies for Plk4-Targeted Therapy.Frontiers in oncology · 2021Review
- Identification of compounds that bind the centriolar protein SAS-6 and inhibit its oligomerization.The Journal of biological chemistry · 2020Article
- Radiation-induced abnormal centrosome amplification and mitotic catastrophe in human cervical tumor HeLa cells and murine mammary tumor EMT6 cells.Journal of clinical biochemistry and nutrition · 2020Article
- Anticancer effects of the PLK4 inhibitors CFI-400945 and centrinone in Ewing's sarcoma cells.Journal of cancer research and clinical oncology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Polo-like kinase 4 (PLK4) is a cell cycle-regulated protein kinase (PK) recruited at the centrosome in dividing cells. Its overexpression triggers centrosome amplification, which is associated with genetic instability and carcinogenesis. In previous work, we established that PLK4 is overexpressed in pediatric embryonal brain tumors (EBT). We also demonstrated that PLK4 inhibition exerted a cytostatic effect in EBT cells. Here, we examined an array of PK inhibitors (CFI-400945, CFI-400437, centrinone, centrinone-B, R-1530, axitinib, KW-2449, and alisertib) for their potential crossover to PLK4 by comparative structural docking and activity inhibition in multiple established embryonal tumor cell lines (MON, BT-12, BT-16, DAOY, D283). Our analyses demonstrated that: (1) CFI-400437 had the greatest impact overall, but similar to CFI-400945, it is not optimal for brain exposure. Also, their phenotypic anti-cancer impact may, in part, be a consequence of the inhibition of Aurora kinases (AURKs). (2) Centrinone and centrinone B are the most selective PLK4 inhibitors but they are the least likely to penetrate the brain. (3) KW-2449, R-1530 and axitinib are the ones predicted to have moderate-to-good brain penetration. In conclusion, a new selective PLK4 inhibitor with favorable physiochemical properties for optimal brain exposure can be beneficial for the treatment of EBT.
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.