Abstract: The present invention provides compositions comprising bisfluoroalkyl-1,4-benzodiazepinone compounds, including compounds of Formula (I) or prodrugs thereof; optionally in combination with an additional cancer therapeutic agent, and methods of use thereof for treating proliferative diseases and disorders such as Desmoid tumors.

Abstract: The present invention provides compositions comprising bisfluoroalkyl-1,4-benzodiazepinone compounds, including compounds of Formula (I) or prodrugs thereof; optionally in combination with an additional cancer therapeutic agent, and methods of use thereof for treating proliferative diseases and disorders such as Desmoid tumors.

Abstract: The present invention provides methods of reducing tumor size, suppressing or inhibiting tumor growth, or prolonging progression-free survival or overall survival in subjects having Notch-activated breast cancer by administering compositions comprising bisfluoroalkyl-1,4-benzodiazepinone compounds, including compounds of Formula (III): or prodrugs thereof, alone or in combination with a composition comprising a cytotoxic agent. Notch-activated breast cancer may be determined by a) Notch-activating genetic alterations in one or more Notch genes, b) overexpression of one or more Notch-regulated genes, c) overexpression of one or more Notch proteins or Notch-regulated proteins, or a combination thereof.

Abstract: The present invention provides compositions comprising bisfluoroalkyl-1,4-benzodiazepinone compounds, including compounds of Formula (I) or prodrugs thereof; in combination with an additional cancer therapeutic agent, and methods of use thereof for treating diseases and disorders such as cancer.

Abstract: The present invention provides compositions comprising bisfluoroalkyl-1,4-benzodiazepinone compounds, including compounds of Formula (I) or prodrugs thereof; in combination with an additional cancer therapeutic agent, and methods of use thereof for treating diseases and disorders such as cancer.

Abstract: Compositions and methods for modulating the activation of nuclear factor ?B (NF-?B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I?B? and/or I?B?. Such compositions may be used for treating diseases associated with NF-?B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Abstract: Compositions and methods for modulating the activation of nuclear factor ?B (NF-?B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I?B? and/or I?B? Such compositions may be used for treating diseases associated with NF-?B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Abstract: Compositions and methods for modulating the activation of nuclear factor ?B (NF-?B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I?B? and/or I?B?. Such compositions may be used for treating diseases associated with NF-?B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Abstract: Compositions and methods for modulating the activation of nuclear factor ?B (NF-?B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I?B? and/or I?B?. Such compositions may be used for treating diseases associated with NF-?B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Abstract: Compositions and methods for modulating the activation of nuclear factor ?B (NF-?B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I?B? and/or I?B?. Such compositions may be used for treating diseases associated with NF-?B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Abstract: Compounds that inhibit ubiquitin-mediated proteolysis of phosphorylated I?B by interfering, directly or indirectly, with the ability of ?-TrCP/E3RS to engage in protein-protein association involving hnRNP-U, are useful as drugs for treating conditions associated with NF-?B activation. Cellular and non-cellular screening methods for identifying such compounds are based on monitoring the association/dissociation of ?-TrCP/E3RS.

Abstract: Compositions and methods for modulating the activation of nuclear factor &kgr;B (NF-&kgr;B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I&kgr;B&agr; and/or I&kgr;B&bgr;. Such compositions may be used for treating diseases associated with NF-&kgr;B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Abstract: Compounds that inhibit ubiquitin-mediated proteolysis of phosphorylated I&kgr;B by interfering, directly or indirectly, with the ability of &bgr;-TrCP/E3RS to engage in protein-protein association involving hnRNP-U, are useful as drugs for treating conditions associated with NF-&kgr;B activation. Cellular and non-cellular screening methods for identifying such compounds are based on monitoring the association/dissociation of &bgr;-TrCP/IE3RS.

Abstract: Compositions and methods for modulating the activation of nuclear factor &kgr;B (NF-&kgr;B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I&kgr;B&agr; and/or I&kgr;B&bgr;. Such compositions may be used for treating diseases associated with NF-&kgr;B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Abstract: Compositions and methods for modulating the activation of nuclear factor &kgr;B (NF-&kgr;B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I&kgr;B&agr; and/or I&kgr;B&bgr;. Such compositions may be used for treating diseases associated with NF-&kgr;B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.