ArticleCancers2019
Wee1 Rather Than Plk1 Is Inhibited by AZD1775 at Therapeutically Relevant Concentrations.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled 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.
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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Pooled it
- Multiple Regulatory Mechanisms of Post-Translational Modifications and Therapeutic Potential of Mitotic Catastrophe.International journal of molecular sciences · 2026Review
- Current progress in targeting mitotic kinases in PDAC.RSC medicinal chemistry · 2025Review
- Azenosertib Is a Potent and Selective WEE1 Kinase Inhibitor with Broad Antitumor Activity Across a Range of Solid Tumors.Molecular cancer therapeutics · 2025Article
- Unveiling an Arpp-19 phosphorylation switch that grants chromosome stability.Communications biology · 2025Article
- Article
- Preparation for mitosis requires gradual CDK1 activation.iScience · 2025Article
- Cyclin E1 overexpression sensitizes ovarian cancer cells to WEE1 and PLK1 inhibition.Oncogene · 2025Article
- Article
- Autophagy modulates the stability of Wee1 and cell cycle G2/M transition.Biochemical and biophysical research communications · 2023Article
- Selective Wee1 Inhibitors Led to Antitumor ActivityACS medicinal chemistry letters · 2023Article
- Development of Cell Permeable NanoBRET Probes for the Measurement of PLK1 Target Engagement in Live Cells.Molecules (Basel, Switzerland) · 2023Article
- Development of Cell Permeable NanoBRET Probes for the Measurement of PLK1 Target Engagement in Live Cells.bioRxiv : the preprint server for biology · 2023Article
- Article
- cGAS-dependent proinflammatory and immune homeostatic effects of the microtubule-targeting agent paclitaxel.Frontiers in immunology · 2023Article
- Friends with Benefits: Chemokines, Glioblastoma-Associated Microglia/Macrophages, and Tumor Microenvironment.International journal of molecular sciences · 2022Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Wee1 kinase is an inhibitor of cyclin-dependent kinase (cdk)s, crucial cell cycle progression drivers. By phosphorylating cdk1 at tyrosine 15, Wee1 inhibits activation of cyclin B-cdk1 (Cdk1), preventing cells from entering mitosis with incompletely replicated or damaged DNA. Thus, inhibiting Wee1, alone or in combination with DNA damaging agents, can kill cancer cells by mitotic catastrophe, a tumor suppressive response that follows mitosis onset in the presence of under-replicated or damaged DNA. AZD1775, an orally available Wee1 inhibitor, has entered clinical trials for cancer treatment following this strategy, with promising results. Recently, however, AZD1775 has been shown to inhibit also the polo-like kinase homolog Plk1 in vitro, casting doubts on its mechanism of action. Here we asked whether, in the clinically relevant concentration range, AZD1775 inhibited Wee1 or Plk1 in transformed and non-transformed human cells. We found that in the clinically relevant, nanomolar, concentration range AZD1775 inhibited Wee1 rather than Plk1. In addition, AZD1775 treatment accelerated mitosis onset overriding the DNA replication checkpoint and hastened Plk1-dependent phosphorylation. On the contrary selective Plk1 inhibition exerted opposite effects. Thus, at therapeutic concentrations, AZD1775 inhibited Wee1 rather than Plk1. This information will help to better interpret results obtained by using AZD1775 both in the clinical and experimental settings and provide a stronger rationale for combination therapies.
Indexed as
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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.