University of Illinois

Andrei Gartel

Senthil Radhakrishnan

The present invention provides methods of utilizing a nucleoside derivative having the chemical formula of Formula (I) to downregulate expression of an anti-apoptotic protein such as survivin in a cell, induce apoptosis in a cell, inhibit angiogenesis in a cell, inhibit binding of p53 to DNA in a cell, inhibit phosphorylation of Akt in a cell and inhibit HIV transcription in a cell, by administering to the cell or tissue an amount of a compound of Formula (I) sufficient to achieve the desired activity. Formula (I): wherein the substituents R, R, R, R, R, R, R, R, Rand Rare as defined in the specification. A particularly preferred nucleoside derivative is ARC (4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo[2,3-d]-pyrimidine-5-carboxamide).

Nucleoside compounds and methods of use thereof

Embodiments of the invention provides, among other things, methods for identifying agents that inhibit oncogenic transcription factors, induce apoptosis, inhibit the growth of transformed cells and cancer cells, and potentiate the effects of other agents that induce apoptosis and that inhibit the growth of transformed cells and cancer cells. Embodiments of the invention further provide compositions useful for the same comprising an agent the inhibits one or more oncogenic transcription factors and an agent that induces apoptosis, particular compositions wherein the apoptotic effect of the combination is greater than either agent by itself. Embodiments of the invention further provide for the use of such agents and compositions to treat cancer. In illustrative embodiments the agents that inhibit transcription factor activity are thiazole antibiotics, such as Siomycin and thiostrepton, and the apoptosis inducing agent is a member of the TNF ligand superfamily, such as TNF-alpha. In illustrative embodiments the cancers are those in which both the FoxM1 and the NF-kB oncogenic pathways are activated.

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Chicago, IL, United States of America

Andrei Gartel