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.

Date of Patent:
Apr. 11, 2017

Filed:

Jun. 03, 2013
Applicants:

H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL (US);

University of Florida Research Foundation, Inc., Gainesville, FL (US);

Inventors:

Daniel M. Sullivan, Lutz, FL (US);

Thomas C. Rowe, Gainesville, FL (US);

David A. Ostrov, Gainesville, FL (US);

Joel G. Turner, Land O'Lakes, FL (US);

Attorneys:
Primary Examiner:
Int. Cl.
CPC ...
A61K 31/122 (2006.01); A61K 31/529 (2006.01); A61K 31/439 (2006.01); A61K 31/5395 (2006.01); A61K 31/4164 (2006.01); A61K 31/519 (2006.01); A61K 31/53 (2006.01); A61K 45/06 (2006.01); C07C 49/633 (2006.01); C07D 233/24 (2006.01); C07D 471/18 (2006.01); C07D 487/16 (2006.01); C07D 487/22 (2006.01);
U.S. Cl.
CPC ...
A61K 31/439 (2013.01); A61K 31/122 (2013.01); A61K 31/4164 (2013.01); A61K 31/519 (2013.01); A61K 31/529 (2013.01); A61K 31/53 (2013.01); A61K 31/5395 (2013.01); A61K 45/06 (2013.01); C07C 49/633 (2013.01); C07D 233/24 (2013.01); C07D 471/18 (2013.01); C07D 487/16 (2013.01); C07D 487/22 (2013.01);
Abstract

Topoisomerase II alpha (topo IIα) is exported from the cell nucleus in human myeloma cells by a chromosome-maintenance protein-1 (CRM1)-dependent mechanism, resulting in topo II inhibitor resistance. The nuclear export signal (NES) of topo IIα is unique, making it a potential target for small molecule inhibitors. Small molecules NES inhibitors were identified, which inhibited binding of topo IIα to the export receptor CRM1. Inhibition was specific to topo IIα as p53 trafficking was unaffected along with topo IIα protein expression and function (decatenation). These topo IIα-specific nuclear export inhibitors may potentially lead to a new approach in circumventing drug resistance in multiple myeloma. The compounds provide a protocol for treating multiple myeloma or an oncogenic disease. Further, the topoisomerase II nuclear export signal inhibitor may be combined with a topoisomerase II inhibitor.


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