ArticleLeukemia2009
Inhibition of KSP by ARRY-520 induces cell cycle block and cell death via the mitochondrial pathway in AML cells.
Article in Leukemia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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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.
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Who cites it
18 citing papers in PubMed, 44 citations in OpenAlex.
- Phase I/II multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD4877 in patients with refractory acute myeloid leukemia.Investigational new drugs · 2012Trial
- Kinesin Spindle Protein (KIF11) in Mitosis and Cancer.International journal of molecular sciences · 2025Review
- SLC25A21 correlates with the prognosis of adult acute myeloid leukemia through inhibiting the growth of leukemia cells via downregulating CXCL8.Cell death & disease · 2024Article
- Article
- NAT10 regulates mitotic cell fate by acetylating Eg5 to control bipolar spindle assembly and chromosome segregation.Cell death and differentiation · 2022Article
- Optical Control of Mitosis with a Photoswitchable Eg5 Inhibitor.Angewandte Chemie (International ed. in English) · 2022Article
- Article
- Thiadiazole derivatives as anticancer agents.Pharmacological reports : PR · 2020Review
- CMPD1 inhibited human gastric cancer cell proliferation by inducing apoptosis and G2/M cell cycle arrest.Biological research · 2018Article
- Kinesin family member 11 contributes to the progression and prognosis of human breast cancer.Oncology letters · 2017Article
- KSP inhibitor SB743921 inhibits growth and induces apoptosis of breast cancer cells by regulating p53, Bcl-2, and DTL.Anti-cancer drugs · 2016Article
- Impact of kinesin Eg5 inhibition by 3,4-dihydropyrimidin-2(1H)-one derivatives on various breast cancer cell features.BMC cancer · 2015Article
- Article
- Identification of cytoskeleton-associated proteins essential for lysosomal stability and survival of human cancer cells.PloS one · 2012Article
- Synthesis and characterization of tritylthioethanamine derivatives with potent KSP inhibitory activity.Bioorganic & medicinal chemistry · 2011Article
- Mitotic catastrophe: a mechanism for avoiding genomic instability.Nature reviews. Molecular cell biology · 2011Review
- Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors.Haematologica · 2010Article
- Leveraging Kinesin Family as Key Regulators of Malignant Progression and the Immunometabolic Niche for Precision Oncology.Technology in cancer research & treatmentReview
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Kinesin spindle protein (KSP), a microtubule-associated motor protein essential for cell cycle progression, is overexpressed in many cancers and is a potential anti-tumor target. We found that inhibition of KSP by a selective inhibitor, ARRY-520, blocked cell cycle progression, leading to apoptosis in acute myeloid leukemia cell lines that express high levels of KSP. Knockdown of p53, overexpression of XIAP and mutation in caspase-8 did not significantly affect sensitivity to ARRY-520, suggesting that the response is independent of p53, XIAP and the extrinsic apoptotic pathway. Although ARRY-520 induced mitotic arrest in both HL-60 and Bcl-2-overexpressing HL-60Bcl-2 cells, cell death was blunted in HL-60Bcl-2 cells, suggesting that the apoptotic program is executed through the mitochondrial pathway. Accordingly, inhibition of Bcl-2 by ABT-737 was synergistic with ARRY-520 in HL-60Bcl-2 cells. Furthermore, ARRY-520 increased Bim protein levels prior to caspase activation in HL-60 cells. ARRY-520 significantly inhibited tumor growth of xenografts in SCID mice and inhibited AML blast but not normal colony formation, supporting a critical role for KSP in proliferation of leukemic progenitor cells. These results demonstrate that ARRY-520 potently induces cell cycle block and subsequent death in leukemic cells via the mitochondrial pathway and has the potential to eradicate AML progenitor cells.
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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.