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

ABSTRACT: 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 (K _d: 24.5 μM) was determined to specifically adduct C573 out of 11 total cysteines on the catalytic domain of NIK, thereby identifying the allos

SUBMITTER: Anderson JJ 

PROVIDER: S-EPMC11843252 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature