University of Louisville Research Foundation

University of Cape Town

Pauline Janet Van Der Watt

John Olaf Trent

Virna Drucille Leaner

Implementations of the present invention include a compound and methods for inhibiting karyopherin beta 1 activity by administering to a patient in need thereof a therapeutically effective amount of a substituted benzoxazepine. The compound of Formula II, 9-[(1-methylpiperidin-3-yl)methoxy]-4-[(6-methylpyridin-2-yl)methyl]-7-(5-methylthiophen-2-yl)-3,5-dihydro-2H-1,4-benzoxazepine or one of its salts, inhibits the import of protein and transcription factors, such as NFAT and P65/NFKB into the nucleus of a cell, and thus has anti-cancer effects enabling the compound to be used for cancer treatment. 

Substituted benzoxazepine for cancer therapy

Compounds, including quinoxaline derivatives of formula I, for use in the treatment of cancer are described. In general, the compounds inhibit the import of proteins and transcription factors such as Kpn&#x3b1;, AP-1, P65, NFAT into the nucleus of a cell by inhibiting the nuclear import protein, Kpn&#x3b2;1. Cancer cells have elevated levels of Kpn&#x3b2;1 and the inhibition of their nuclear import activity induces cell apoptosis. The administration of an effective amount of any one of the compounds results in cell apoptosis in cancer cells, while non-cancer cells are substantially unaffected by the inhibition of Kpn&#x3b2;1's nuclear import activity. 

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Observatory, South Africa

Pauline Janet Van Der Watt