Abstract: In accordance with the present invention, it has been discovered that compounds which modulate the ?-secretase enzyme to make more of the shorter, less toxic and less aggregation-prone A? peptides (such as A?37 and A?38), while making less of the longer and more toxic and aggregation-prone AB peptides (such as AB40 and AB42) are useful as gamma-secretase modulators. In addition, these GSM compounds have further been discovered to have the selective property of modulating the formation of various AB peptides, while not inhibiting the overall activity of the ?-secretase enzyme. Thus, such compounds do not impede other critical functions of the ?-secretase enzyme, such as generating fragments from Notch that appear to control gene expression and cell differentiation. Therefore, in accordance with the present invention, there are provided screening assays useful for determining whether test compounds have GSM activity; accordingly, invention assays facilitate the identification of new gamma-secretase modulators.

Abstract: In accordance with the present invention, it has been discovered that compounds which modulate the ?-secretase enzyme to make more of the shorter, less toxic and less aggregation-prone A? peptides (such as A?37 and A?38), while making less of the longer and more toxic and aggregation-prone AB peptides (such as AB40 and AB42) are useful as gamma-secretase modulators. In addition, these GSM compounds have further been discovered to have the selective property of modulating the formation of various AB peptides, while not inhibiting the overall activity of the ?-secretase enzyme. Thus, such compounds do not impede other critical functions of the ?-secretase enzyme, such as generating fragments from Notch that appear to control gene expression and cell differentiation. Therefore, in accordance with the present invention, there are provided screening assays useful for determining whether test compounds have GSM activity; accordingly, invention assays facilitate the identification of new gamma-secretase modulators.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Survivin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Survivin. Methods of using these compounds for modulation of Survivin expression and for treatment of diseases associated with expression of Survivin are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Survivin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Survivin. Methods of using these compounds for modulation of Survivin expression and for treatment of diseases associated with expression of Survivin are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of FLIP-c. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding FLIP-c. Methods of using these compounds for modulation of FLIP-c expression and for treatment of diseases associated with expression of FLIP-c are provided.

Abstract: Compositions and methods are provided for modulating the expression of novel anti-apoptotic bcl-2-related proteins. Antisense oligonucleotides targeted to nucleic acids encoding the human novel anti-apoptotic bcl-2-related proteins A1 and mcl-1 are preferred. Methods of using these compounds for modulation of novel anti-apoptotic bcl-2-related protein expression and for treatment of diseases associated with expression of novel anti-apoptotic bcl-2-related proteins are also provided. Also provided are methods of using these compounds for promoting apoptosis and for treatment of diseases for which promotion of apoptosis is desired.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Cellular Inhibitor of Apoptosis-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Cellular Inhibitor of Apoptosis-1. Methods of using these compounds for induction of cellular apoptosis are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Survivin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Survivin. Methods of using these compounds for modulation of Survivin expression and for treatment of diseases associated with expression of Survivin are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Cellular Inhibitor of Apoptosis-2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Cellular Inhibitor of Apoptosis-2. Methods of using these compounds for modulation of Cellular Inhibitor of Apoptosis-2 expression and for treatment of diseases associated with expression of Cellular Inhibitor of Apoptosis-2 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Survivin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Survivin. Methods of using these compounds for modulation of Survivin expression and for treatment of diseases associated with expression of Survivin are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Survivin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Survivin. Methods of using these compounds for modulation of Survivin expression and for treatment of diseases associated with expression of Survivin are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Survivin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Survivin. Methods of using these compounds for modulation of Survivin expression and for treatment of diseases associated with expression of Survivin are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of X-linked inhibitor of apoptosis. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding X-linked inhibitor of apoptosis. Methods of using these compounds for modulation of X-linked inhibitor of apoptosis expression and for treatment of diseases associated with expression of X-linked inhibitor of apoptosis are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Survivin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Survivin. Methods of using these compounds for modulation of Survivin expression and for treatment of diseases associated with expression of Survivin are provided.

Abstract: Compositions and methods are provided for modulating the expression of novel anti-apoptotic bcl-2-related proteins. Antisense oligonucleotides targeted to nucleic acids encoding the human novel anti-apoptotic bcl-2-related proteins A1 and mcl-1 are preferred. Methods of using these compounds for modulation of novel anti-apoptotic bcl-2-related protein expression and for treatment of diseases associated with expression of novel anti-apoptotic bcl-2-related proteins are also provided. Also provided are methods of using these compounds for promoting apoptosis and for treatment of diseases for which promotion of apoptosis is desired.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of microtubule-associated protein 4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding microtubule-associated protein 4. Methods of using these compounds for modulation of microtubule-associated protein 4 expression and for treatment of diseases associated with expression of microtubule-associated protein 4 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Cellular Inhibitor of Apoptosis-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Cellular Inhibitor of Apoptosis-1. Methods of using these compounds for modulation of Cellular Inhibitor of Apoptosis-1 expression and for treatment of diseases associated with expression of Cellular Inhibitor of Apoptosis-1 are provided.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Cellular Inhibitor of Apoptosis-2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Cellular Inhibitor of Apoptosis-2. Methods of using these compounds for modulation of Cellular Inhibitor of Apoptosis-2 expression and for treatment of diseases associated with expression of Cellular Inhibitor of Apoptosis-2 are provided.