ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
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- Pharmacophore-Based Structure Optimization ofACS medicinal chemistry letters · 2025Article
- Kinesin Spindle Protein (KIF11) in Mitosis and Cancer.International journal of molecular sciences · 2025Review
- Paclitaxel neurotoxicity is triggered by epidermal EG5-dependent microtubule fasciculation and X-ROS formation.Research square · 2025Article
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- Identifying and characterising promising small molecule inhibitors of kinesin spindle protein using ligand-based virtual screening, molecular docking, molecular dynamics and MM‑GBSA calculations.Journal of computer-aided molecular design · 2024Article
- Design, synthesis, molecular docking, andSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Neutrophil elastase as a versatile cleavage enzyme for activation of αvβ3 integrin-targeted small molecule drug conjugates with different payload classes in the tumor microenvironment.Frontiers in pharmacology · 2024Article
- Deciphering breast cancer prognosis: a novel machine learning-driven model for vascular mimicry signature prediction.Frontiers in immunology · 2024Article
- Design and synthesis of new 1,2,4-oxadiazole/quinazoline-4-one hybrids with antiproliferative activity as multitargeted inhibitors.Frontiers in chemistry · 2024Article
- Design, Synthesis, Antitumour Evaluation, and In Silico Studies of Pyrazolo-[1,5-Molecules (Basel, Switzerland) · 2023Article
- A Comprehensive Study on the Electrostatic Properties of Tubulin-Tubulin Complexes in Microtubules.Cells · 2023Article
- Combined Inhibition of KIF11 and KIF15 as an Effective Therapeutic Strategy for Gastric Cancer.Current cancer drug targets · 2023Article
- Role of motor proteins in human cancers.Saudi journal of biological sciences · 2022Review
- Kinesin spindle protein inhibitors in cancer: from high throughput screening to novel therapeutic strategies.Future science OA · 2022Review
- Article
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15 authors.
Funding
Abstract
purposeIspinesib (SB-715992) is a potent inhibitor of kinesin spindle protein, a kinesin motor protein essential for the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. Clinical studies of ispinesib have shown a 9% response rate in patients with locally advanced or metastatic breast cancer and a favorable safety profile without significant neurotoxicities, gastrointestinal toxicities, or hair loss. To better understand the potential of ispinesib in the treatment of breast cancer, we explored the activity of ispinesib alone and in combination with several therapies approved for the treatment of breast cancer. EXPERIMENTAL
designWe measured the ispinesib sensitivity and pharmacodynamic response of breast cancer cell lines representative of various subtypes in vitro and as xenografts in vivo and tested the ability of ispinesib to enhance the antitumor activity of approved therapies.
resultsIn vitro, ispinesib displayed broad antiproliferative activity against a panel of 53 breast cell lines. In vivo, ispinesib produced regressions in each of five breast cancer models and tumor-free survivors in three of these models. The effects of ispinesib treatment on pharmacodynamic markers of mitosis and apoptosis were examined in vitro and in vivo, revealing a greater increase in both mitotic and apoptotic markers in the MDA-MB-468 model than in the less sensitive BT-474 model. In vivo, ispinesib enhanced the antitumor activity of trastuzumab, lapatinib, doxorubicin, and capecitabine and exhibited activity comparable with paclitaxel and ixabepilone.
conclusionsThese findings support further clinical exploration of kinesin spindle protein inhibitors for the treatment of breast cancer.
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