发明名称 |
Small molecule E2F inhibitor |
摘要 |
A small molecular inhibitor of E2F (HLM006474) was identified using a computer-based virtual screen and the known crystal structure of the DNA bound E2F4/DP2 heterodimer. Treatment of multiple cell lines resulted in the loss of intracellular E2F4 DNA-binding activity. Overnight exposure to HLM006474 resulted in down regulation of total E2F4 protein as well as several known E2F targets. The effects of treatment on different cell lines included a reduction in cell proliferation and an increase in apoptosis. Apoptosis was induced in a manner distinct from cisplatin and doxorubicin. E2F4-null MEFs (mouse embryo fibroblasts) were less sensitive than wildtype counterparts to the apoptosis-inducing activity of the compound revealing its biological specificity. A375 cells were extremely sensitive to the apoptosis-inducing activity of the compound in two-dimensional culture and HLM006474 was a potent inhibitor of melanocytes proliferation and subsequent invasion in a three-dimensional tissue culture model system. |
申请公布号 |
US8202886(B2) |
申请公布日期 |
2012.06.19 |
申请号 |
US20100872263 |
申请日期 |
2010.08.31 |
申请人 |
CRESS DOUGLAS W.;MA YIHONG;H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.;UNIVERSITY OF SOUTH FLORIDA |
发明人 |
CRESS DOUGLAS W.;MA YIHONG |
分类号 |
A61K31/4709 |
主分类号 |
A61K31/4709 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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