Novel Fluoroquinolone-based Compounds with Anticancer Activity
- 详细技术说明
- Dr. Kerns and Dr. Hiasa have discovered novel fluoroquinolones that have anticancer activity. These compounds target type I topoisomerases instead of type II topoisomerases, providing a novel mechanism of action. These compounds inhibit topoisomerase activities without generating double-strand breaks. Thus, the treatment with these compounds is not likely to cause therapy-related acute myeloid leukemia. In vitro tests revealed their significant anti-proliferative activities against many cancer cell lines and an in vivo study showed their efficacy in a colon cancer xenograft model. It is also anticipated that these compounds will be effective against cancers that have developed a resistance to cancer drugs like etoposide. Advantages Target topoisomerase I with a unique mechanism of actionDo not lead to double-strand break generation – better safety profileStrong in vitro data against a wide variety of cancer cell linesPromising in vivo efficacy data in a colon cancer xenograft model.
- *Abstract
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Fluoroquinolones, clinically important antibacterial drugs, normally target the bacterial type II topoisomerases. They bind to covalent topoisomerase-DNA catalytic intermediates and cause the generation of double-strand breaks. A few fluoroquinolones that target human topoisomerase II, a eukaryotic type II topoisomerase, as well as clinically successful topoisomerase II-targeting anticancer drugs, such as etoposide and doxorubicin, also utilize the same mechanism to generate double-strand breaks and induce cell death. However, double-strand break generation is also the cause of therapy-related acute myeloid leukemia. Due to this dangerous side effect of the treatment, there is an unmet need to develop topoisomerase inhibitors that utilize a different mechanism and have a better safety profile.
- *Licensing
- Email: uirf-marketing@uiowa.eduPhone: (319) 335-4546
- 国家/地区
- 美国
