The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Jun. 19, 2012
Filed:
Aug. 31, 2010
Douglas W. Cress, Lutz, FL (US);
Yihong MA, Lutz, FL (US);
Douglas W. Cress, Lutz, FL (US);
Yihong Ma, Lutz, FL (US);
H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL (US);
University of South Florida, Tampa, FL (US);
Abstract
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.