NIKinh (NIK inhibitor) is a highly specific, potent NF-κB-inducing kinase (NIK) inhibitor with IC50 of 5.12 uM in ADP-Glo assay.
NIKin hinhibits NIK's ability to phosphorylate a substrate protein in vitro in an ATP-dependent manner (ADP-Glo assay).
NIKinh also reduced EZH2 expression, a downstream target of NIK, in a dose-dependent manner in a melanoma cell line characterized by upregulation of non-canonical pathway (A375), and concomitantly increased the expression of CDKN1A/p21.
NIKinh decreased cleavage of p100 into p52, and EZH2 at the protein level in A375 cells, lung cancer cells (A549), and freshly isolated patient melanoma cells (C12.06).
NIKinh single treatment and combined with anti-PD-1 resulted in significantly increased survival of up to 60% and 70% of the plck-GAPDH tumor-engrafted mice, respectively.
NIKinh treatment ex vivo reduced the growth of CD4+ Tfh cells from hAITL biopsies upon TCR stimulation, whereas healthy CD4+ T cells remained unaffected.