Biochem/physiol Actions

Amgen16 is an NF-κB-inducing kinase (NIK) inhibitor that selectively disrupts noncanonical NF-κB activation in U-2 OS cells (lymphotoxin β receptor LTβR-/TWEAK recetor FN14-mediated p52 nuclear translocation IC50 = 417 nM/2.517 µM) without affecting canonical NF-κB activation (TNF-α-stimulated p65 (RelA) nuclear translocation IC50 >30 µM). Likewise, Amgen16 (1 µM, 30 min pretreatment) selectively inhibits NFKB2 (p100) mRNA production upon noncanonical NF-κB activation (by 84%; 20 ng/mL TWEAK for 4 h), while exhibiting much smaller effect against canonical NF-κB stimulator-induced NFKB2 production (by 36%; 10 ng/mLTNFα for 4 h).