MLN120B is a selective and ATP competitive IKKβ inhibitor (IC50: 60 nM).

IKKβ:60 nM

MLN120B几乎完全阻断了MM.1S、U266和INA6细胞的生长刺激，以及由于多发性骨髓瘤细胞与BMSCs粘附所诱导的BMSCs中IL-6的分泌[1]。此外，MLN120B对由LPS引起的RAW267.4细胞中NF-κB激活显示出抑制效果。对于转染了NF-κB2-luc2、IL8-luc2或TNF-AIP3-luc2报告基因的细胞，MLN120B的IC50值分别为1.4、14.8或27.3 μM[3]。

MLN120B（50 mg/kg，口服）在体内抑制人类多发性骨髓瘤细胞的生长[1]。MLN120B（12 mg/kg，每日两次，口服）以剂量依赖的方式抑制爪肿胀，并显著防止因关节炎引起的体重减轻以及软骨和骨骼侵蚀[2]。

Multiple myeloma cells are cultured with MLN120B, harvested, washed, and lysed using lysis buffer [50 mM Tris-HCl (pH 7.4), 150 mM NaCl, 1% NP40, 5 mM EDTA, 5 mM NaF, 2 mM Na3VO4, 1 mM phenylmethylsulfonyl fluoride, 5 μg/mL leupeptin, 5 μg/mL aprotinin]. Whole-cell lysates are subjected to Western blotting using phosphorylated IκBα, IκBα, phosphorylated p65 NF-κB, and p65 NF-κB antibodies [1].

Human fetal long bone grafts are implanted into SCID mice (SCID-hu mice). Approximately 4 weeks following bone implantation, 2.5×10^6 INA6 multiple myeloma cells in 50 μL PBS is injected directly into human bone within SCID-hu hosts. Soluble human IL-6 receptor (shuIL-6R) released from INA6 cells is assessed in mouse sera by ELISA as in our prior studies. Mice are treated orally with vehicle alone or MLN120B 50 mg/kg (twice daily) for 3 weeks after the detection of measurable shuIL-6R in mouse sera [1].