Compounds and methods for modulating activation of NF-κB
AssigneeSignal Pharmaceuticals, LLC
InventorsAnthony M. Manning, Frank Mercurio, Sharon Amit, Yinon Ben-Neriah, Matti Davis, Ada Hatzubai, Avraham Yaron, Irit Alkalay, Aaron Ciechanover
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Abstract
Compositions and methods for modulating the activation of nuclear factor κB (NF-κB) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated IκBα and/or IκBβ. Such compositions may be used for treating diseases associated with NF-κB activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.
Claims7
An isolated polypeptide comprising SEQ ID NO:16 or a truncated portion thereof of at least 50 amino acid residues wherein said portion retains the ability to enhance ubiquitination of phosphorylated IκB.
An isolated polypeptide comprising SEQ ID NO:16 or a truncated portion thereof of at least 200 amino acid residues wherein said portion retains the ability to enhance ubiquitination of phosphorylated IκB.
An isolated polypeptide comprising a variant of SEQ ID NO:16 that differs therefrom at no more than 15% of the amino acid residues of SEQ ID NO:16 wherein said variant retains the ability to enhance ubiquitination of phosphorylated IκB.
An isolated polypeptide comprising a variant of SEQ ID NO:16 that differs therefrom at no more than 10% of the amino acid residues of SEQ ID NO:16 wherein said variant retains the ability to enhance ubiquitination of phosphorylated IκB.
An isolated polypeptide comprising a variant of SEQ ID NO:16 that differs therefrom by deletion of amino acid residues 122-168 of SEQ ID NO:16 or a truncated portion of said variant wherein said portion retains the ability to bind to phosphorylated IκB and inhibits ubiquitination of phosphorylated IκB.
An isolated polypeptide comprising a truncated portion of SEQ ID NO:16 comprising from 50 to 250 residues of SEQ ID NO:16 wherein said portion retains the ability to bind to phosphorylated IκB and inhibits ubiquitination of phosphorylated IκB.
An isolated polypeptide comprising a truncated portion of SEQ ID NO:16 comprising from 10 to 374 residues of SEQ ID NO:16 wherein said portion retains the ability to bind to phosphorylated IκB and inhibits ubiquitination of phosphorylated IκB.
Dependencies are inferred from the claim text.