NIK inhibitor 2

NIK inhibitor 2 is a selective small molecule inhibitor of NF-κB-inducing kinase (NIK, also known as MAP3K14), originally developed by Amgen. It was identified as a potent and selective inhibitor of the non-canonical (alternative) NF-κB pathway. In preclinical studies, particularly in multiple myeloma (MM) models, NIK inhibitor 2 demonstrated selective cytotoxicity against cell lines harboring NIK-dependent NF-κB activation, such as those with NIK over-expression or mutations in NIK-regulatory proteins (e.g., TRAF2, TRAF3, BIRC2/3). By inhibiting NIK, the compound prevents the processing of p100 to p52, thereby suppressing the activation of the non-canonical NF-κB pathway and inducing apoptosis in NIK-dependent cancer cells. Research has shown that NIK inhibitor 2 can act synergistically with IKKβ inhibitors or corticosteroids like dexamethasone to enhance anti-tumor activity in myeloma.

Other names

NIK SMI2Amgen NIK inhibitor 2