ArticleOncotarget2015
Cenp-E inhibitor GSK923295: Novel synthetic route and use as a tool to generate aneuploidy.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Pretreatment Chromosomal Instability Correlates With Radiation Sensitivity in Squamous Cell Cancers.International journal of radiation oncology, biology, physics · 2026Article
- CTCF maintains centromere function and mitotic fidelity.Journal of cell science · 2026Article
- Cell-APP: A generalizable method for cell annotation and cell-segmentation model training.Molecular biology of the cell · 2025Article
- Cell-APP: A generalizable method for cell annotation and cell-segmentation model training.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic Heritability of Cell Plasticity Drives Cancer Drug Resistance through a One-to-Many Genotype-to-Phenotype Paradigm.Cancer research · 2025Article
- Quantitative Proteomic Analysis Reveals Different Functional Subtypes amongJournal of proteome research · 2025Article
- The Overexpression of Collagen Receptor DDR1 is Associated With Chromosome Instability and Aneuploidy in Diffuse Large B-Cell Lymphoma.Journal of cellular and molecular medicine · 2025Article
- Centromeres in cancer: Unraveling the link between chromosomal instability and tumorigenesis.Medical oncology (Northwood, London, England) · 2024Review
- Spatial control of the APC/C ensures the rapid degradation of cyclin B1.The EMBO journal · 2024Article
- Article
- A survey of chromosomal instability measures across mechanistic models.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A conserved CENP-E region mediates BubR1-independent recruitment to the outer corona at mitotic onset.Current biology : CB · 2024Article
- Maximizing Anticancer Response with MPS1 and CENPE Inhibition Alongside Apoptosis Induction.Pharmaceutics · 2023Article
- Article
- A survey of CIN measures across mechanistic models.bioRxiv : the preprint server for biology · 2023Article
- Tetraploidy-linked sensitization to CENP-E inhibition in human cells.Molecular oncology · 2023Article
- CTCF is essential for proper mitotic spindle structure and anaphase segregation.bioRxiv : the preprint server for biology · 2023Article
- Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly.Nature communications · 2022Article
- TP53 loss initiates chromosomal instability in fallopian tube epithelial cells.Disease models & mechanisms · 2021Article
- Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts.Genes · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Aneuploidy is a common feature of cancer, with human solid tumour cells typically harbouring abnormal chromosome complements. The aneuploidy observed in cancer is often caused by a chromosome instability phenotype, resulting in genomic heterogeneity. However, the role aneuploidy and chromosome instability play in tumour evolution and chemotherapy response remains poorly understood. In some contexts, aneuploidy has oncogenic effects, whereas in others it is anti-proliferative and tumour-suppressive. Dissecting fully the role aneuploidy plays in tumourigenesis requires tools and facile assays that allow chromosome missegregation to be induced experimentally in cells that are otherwise diploid and chromosomally stable. Here, we describe a chemical biology approach that induces low-level aneuploidy across a large population of cells. Specifically, cells are first exposed to GSK923295, an inhibitor targeting the mitotic kinesin Cenp-E; while the majority of chromosomes align at the cell's equator, a small number cluster near the spindle poles. By then driving these cells into anaphase using AZ3146, an inhibitor targeting the spindle checkpoint kinase Mps1, the polar chromosomes are missegregated. This results in, on average, two chromosome missegregation events per division, and avoids trapping chromosomes in the spindle midzone, which could otherwise lead to DNA damage. We also describe an efficient route for the synthesis of GSK923295 that employs a novel enzymatic resolution. Together, the approaches described here open up new opportunities for studying cellular responses to aneuploidy.
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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.