Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKK-epsilon) (IKK-epsilon)

Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKK-epsilon), also known as IKK-i, is a non-canonical serine/threonine kinase belonging to the IKK family that plays a dual role in innate immunity and oncogenesis [1, 3]. It is a key mediator of the antiviral response, where it phosphorylates interferon regulatory factors IRF3 and IRF7 to trigger the production of type I interferons [5, 9]. Beyond its physiological role, IKK-epsilon is a recognized oncogene frequently overexpressed or amplified in various malignancies, including breast, lung, and prostate cancers, where it drives cell survival and proliferation by activating the AKT and NF-kappaB pathways [2, 8, 10]. Additionally, IKK-epsilon is implicated in metabolic disorders; its induction in adipose tissue and liver during obesity promotes chronic inflammation and insulin resistance [4, 11]. Due to its involvement in both cancer progression and metabolic dysfunction, IKK-epsilon is an attractive therapeutic target, with small-molecule inhibitors like amlexanox being evaluated for their potential to treat these conditions and overcome therapeutic resistance [2, 13].

Other names

I-kappa-B kinase epsilonIKK-epsilonIKK-iIKK-EIKBKEInducible I kappa-B kinaseIKK-related kinase epsilon

ATP-competitive inhibition of the IKK-epsilon kinase domain, which prevents the phosphorylation of downstream substrates including IRF3, IRF7, and AKT [2, 4, 8].