MLN120B

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

MLN120B 是一种选择性 ATP 竞争性 IKKβ 抑制剂 (IC50: 60 nM)。MLN120B 几乎完全阻断多发性骨髓瘤细胞粘附诱导的 MM.1S、U266 和 INA6 细胞生长的刺激，以及 BMSC 的 IL-6 分泌骨髓间充质干细胞[1]。 MLN120B 对 RAW267.4 细胞中 LPS 诱导的 NF-κB 激活具有抑制作用。

MLN120B is a selective and ATP competitive IKKβ inhibitor (IC50: 60 nM).MLN120B almost completely blocks the 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 . MLN120B shows an inhibitory effect on LPS induced NF-κB activation in RAW267.4 cells. The IC50 values of MLN120B is 1.4, 14.8 or 27.3 μM for NF-κB2-luc2, IL8-luc2 or TNF-AIP3-luc2 reporter transfected cells, respectively.MLN120B (50 mg/kg, p.o.) inhibits human multiple myeloma cell growth in vivo. MLN120B (12 mg/kg twice daily, p.o.) inhibits paw swelling in a dose-dependent manner and offers significant protection against arthritis-induced weight loss as well as cartilage and bone erosion.

MLB120B (0-20 μM; 90 minutes) inhibits phosphorylation and degradation of IκB in RPMI 8226 and INA6 cells; however, no significant inhibition is observed in MM.1S cells.MLB120B (1.25-20 μM; 90 minutes) completely abrogates TNF-a-induced phosphorylation and degradation of IκB in a dosedependent fashion. Phosphorylation of p65 NF-κB induced by TNF-a is also blocked by MLN120B.MLN120B inhibits proliferation of multiple myeloma cell lines. MM.1S, MM.1R, RPMI 8226, RPMI-LR5, RPMI-Dox40, U266, and INA6 cells. Five percent to fifty percent and 18% to 70% inhibition in proliferation is observed at doses >20 uM and [3H]thymidine uptake, respectively.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.MLN120B shows an inhibitory effect on LPS induced NF-κB activation in RAW267.4 cells. The IC50 values of MLN120B is 1.4 μM, 14.8 μM or 27.3 μM for NF-κB2-luc2, IL8-luc2 or TNF-AIP3-luc2 reporter transfected cells, respectively. Western Blot Analysis Cell Line:MM.1S cells Concentration:1.25-20 μM Incubation Time:90 minutes Result:Inhibited p- IκB and p-P65 expression in a dose-dependent manner.Cell Viability Assay Cell Line:Multiple myeloma cell lines: MM.1S, MM.1R, RPMI 8226, RPMI-LR5, RPMI-Dox40, U266, and INA6 cells Concentration:1.25 μM-20 μM Incubation Time:72 hours Result:Inhibits proliferation of multiple myeloma cell lines.

MLN120B (oral administration; 50 mg/kg; twice daily; 3 weeks) induces a reduction of shuIL-6R, marker of tumor growth, marker of tumor growth. It also leads to a rend toward prolonged survival in animals treated versus control.MLN120B (oral administration; 1-30 mg/kg; twice daily; 3 weeks)inhibits paw swelling in a dose-dependent manner and offers significant protection against arthritis-induced weight loss as well as cartilage and bone erosion. NF-κB activity in arthritic joints is also reduced after MLN120B administration. Animal Model:Two-month-old female Lewis rats Dosage:30 mg/kg, 10 mg/kg, 3 mg/kg, or 1 mg/kg Administration:Oral administration; twice daily; 3 weeks Result:Protected against bone and cartilage destruction in a rat model.Animal Model:SCID mice implanted with human fetal bone chips and then INA6 cells are directly injected into mice Dosage:50 mg/kg Administration:Oral administration; twice daily; 3 weeksResult:Inhibited human multiple myeloma cell growth in vivo.

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Immunology/Inflammation

IκB kinase (IKK)

IKKβ

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783348-36-7

366.8

C19H15ClN4O2

>98% (HPLC)

DMSO:30 mg/mL (81.78 mM);Water:Insoluble

O=C(C1=CC=CN=C1C)NC2=C(OC)C(Cl)=CC3=C2NC4=C3C=CN=C4

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(-20℃)

With Ice Pack

≥ 2 years