MLN120B is an effective, ATP-competitive, and orally available inhibitor of IKKβ, demonstrating an IC50 of 60 nM. MLN120B inhibits multiple myeloma cell growth in vitro and in vivo and also can be used for the research of rheumatoid arthritis[1].[2].
体内研究
With oral administration at 50 mg/kg twice daily for three weeks, MLN120B leads to a decrease in shuIL-6R, a marker of tumor growth, and suggests a trend towards extended survival in treated animals compared to controls[1].
When administered orally at doses ranging from 1 to 30 mg/kg twice daily for three weeks, MLN120B dose-dependently reduces paw swelling and significantly protects against arthritis-induced weight loss, as well as cartilage and bone erosion. Additionally, NF-κB activity in arthritic joints is decreased following MLN120B treatment[2].
体外研究
Treatment with MLN120B (ranging from 0 to 20 μM for 90 minutes) results in the inhibition of phosphorylation and degradation of IκB in RPMI 8226 and INA6 cells, though no significant effects are noted in MM.1S cells[1].
At dosages between 1.25 and 20 μM for 90 minutes, MLN120B entirely blocks TNF-alpha-induced phosphorylation and degradation of IκB in a dose-responsive manner, also inhibiting the phosphorylation of p65 NF-κB triggered by TNF-alpha[1].
LN120B inhibits the proliferation of various multiple myeloma cell lines including MM.1S, MM.1R, RPMI 8226, RPMI-LR5, RPMI-Dox40, U266, and INA6, with observed proliferation inhibitions ranging from 5% to 70% at doses above 20 μM, as measured by cell growth rates and [3H]thymidine uptake[1].
In vitro, MLN120B (1.25-40 μM; 72 hours) almost completely blocks stimulation of MM.1S, U266, and INA6 cell growth, as well as IL-6 secretion from BMSCs, induced by multiple myeloma cell adherence to BMSCs[1].
MLN120B exhibits an inhibitory action on LPS-induced NF-κB activation in RAW267.4 cells, with IC50 values of 1.4 μM, 14.8 μM, and 27.3 μM for NF-κB2-luc2, IL8-luc2, or TNF-AIP3-luc2 reporter-transfected cells, respectively[3].
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