Identification of a novel allosteric binding site on the catalytic domain of NF-κB inducing kinase (NIK).

• Tác giả: Jared J Anderson, Daniel A Harki
• Ngôn ngữ: eng
• Thông tin xuất bản: England : RSC medicinal chemistry , 2025
• Bộ sưu tập: NCBI
• ID: 672754

Tóm tắt

NF-κB inducing kinase (NIK) is the central regulatory component of noncanonical NF-κB signalling and has been implicated in a variety of cancers and immune disorders. While NIK has been pursued as a target for such diseases through the design of orthosteric inhibitors, these inhibitors have not resulted in an approved drug. To develop new modalities for NIK-targeting by small molecules, we recently reported a class of chromanol fragments that bind to an unknown allosteric site on the catalytic domain of NIK. Here we report the design of a covalent probe to identify the location of this allosteric binding site. Acrylamide probe 2 (