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Fluorescent CDK Inhibitors for the Treatment and Diagnosis of Cancer

技术优势

Compounds of the invention demonstrate higher % inhibition of CDK2/A and CDK2/E than known CDK2 inhibitor, seliciclibAfluorescent label allow these compounds to be used as both atherapeutic to treat cancer and a diagnostic to detect cancerous cellsand monitor treatmentCell growth inhibition potency (IC50) in certain cancer cell lines is superior to known CDK inhibitors purvanalol and seliciclib

详细技术说明

The invention describes promising new fluorescent small moleculepharmaceutical leads for the treatment of cancer by inhibition ofcyclin dependant kinase (CDK). The novel compounds are more potent thanknown CDK inhibitors, purvalanols A and B as well as phase II clinicaldrug candidate, roscovitine (seliciclib). These compounds areespecially potent inhibitors of CDK2 isoforms and effectively arresttumor cells in the G2/M phase. These new compounds may be an effectivenew tool for not only for treating, but also diagnosing cancer andmonitoring cancer therapy.

*Abstract

*Stage of Development

Growth inhibition, IC50 values were obtained for compounds using the 48hours WST-1 assay in ER negative and ER positive breast cancer celllines. Inhibition of cell cycle protein kinases: CDK1/B, CDK2/A,CDK2/E, CDK3/E and CDK7/CyclinH/MATI, by compounds of the inventionwere compared with commercially available CDK inhibitors purvalanols Aand B and roscovitine. The compounds almost completely inhibited CDK2/Eat nanomolar range. Fluorescence micrographs of breast cancer cellcultures showed that the compounds localized in the cancer cells.

国家/地区

美国