MLN120B
(Synonyms: N-(6-氯-7-甲氧基-9H-吡啶并[3,4-B]吲哚-8-基)-2-甲基-3-吡啶甲酰胺,ML120B;MLN 120B;MLN-120B) 目录号 : GC14989
An IKKβ inhibitor
Cas No.:783348-36-7
Sample solution is provided at 25 µL, 10mM.
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MLN120B is a potent and effective inhibitor of IκB kinase beta subunit (IKKβ) with IC50 value of 20 μM [1].
IKK is an enzyme complex which is a part of the upstream of NF-κB signal transduction cascade. It is composed of three subunits, including IKKα, IKKβ and IKKγ. The IKKβ subunit is able to phosphorylate IκBα protein. Normally, IκBα protein inactivate NF-κB transcription factors and keep them sequestering in inactive state in the cytoplasm. However, once IκBα protein is phosphorylated by IKKβ subunit, the IκBα protein will be dissociated from NF-κB transcription factor and thus remove the inactivation effect. Therefore, the transcription of NF-κB will be activated. This signaling pathway is involved in many immune and inflammatory processes.
In multiple myeloma cell line RPMI 8226 and INA 6, treatment of MLN120B resulted in the dose-dependent inhibition of IKKβ-induced IκBα protein phosphorylation and subsequent NF-κB activation. Additionally, it was observed that MLN120B was able to block TNF-α-induced NF-κB activation in MM.1S cell line. These observations suggested the inhibitory action of MLN120B on IKKβ. [1].
In mouse model, polyarthritis was introduced in footpads, where IKKβ-induced NF-κB activation might result in a serial of advert effects. Oral administration of MLN120B (12 mg/kg twice daily) inhibited paw swelling in a dose-dependent manner, and offered protection against arthritis-induced weight loss. Therefore, it could be implied that MLN120B was able to inhibit IKKβ-induced NF-κB activation [2].
References:
[1]. Hideshima T, Neri P, Tassone P. MLN120B, a novel IkappaB kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo. Clin Cancer Res. 2006, 12(19): 5887-5894.
[2]. Schopf L, Savinainen A, Anderson K. IKKbeta inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritis. Arthritis Rheum. 2006, 54(10): 3163-3173.
| Cell experiment [1]: | |
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Cell lines |
RPMI 8226 and U266 human multiple myeloma cells |
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Preparation method |
The solubility of this compound in DMSO is >13.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1.25-20μmol/L for 90 minutes |
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Applications |
In RPMI 8226 and U266 human multiple myeloma cells, TNF-α (tumor necrosis factor-a)-induced phosphorylation and degradation of IκBα were completely abrogated by MLN120B in a dose dependent fashion. Phosphorylation of p65 NF-κB (Nuclear factor-κB) induced by TNF-α was also blocked by MLN120B. Importantly, MLN120B inhibited both IL-6 secretion from BMSCs (bone marrow stromal cells) triggered by multiple myeloma cell adhesion and proliferation of multiple myeloma cells adherent to BMSCs. MLN120B triggered 25% to 90% growth inhibition in a dose-dependent fashion in multiple myeloma cell lines, which is not overcome by growth and antiapoptotic factors (IL-6 or IGF-I). |
| Animal experiment [2]: | |
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Animal models |
Rat adjuvant-induced arthritis model (Two-month-old female Lewis rats) |
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Dosage form |
orally as a suspension delivered via a gavage needle, at 30 mg/kg, 10 mg/kg, 3 mg/kg |
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Application |
In Lewis rats, Animals receiving MLN120B showed a dose-dependent reduction of arthritis development, as measured by paw swelling, compared with vehicle-treated controls. Administration of MLN120B at a dosage of 30 mg/kg twice daily offered significant protection against weight loss compared with arthritic controls. These results indicated bone and cartilage destruction and pannus development were the features most improved with MLN120B administration. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Hideshima T, Neri P, Tassone P. MLN120B., et al. a novel IkappaB kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo. Clin Cancer Res. 2006, 12(19): 5887-5894. [2]. Schopf L, Savinainen A, Anderson K., et al. IKKbeta inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritis. Arthritis Rheum. 2006, 54(10): 3163-3173. | |
| Cas No. | 783348-36-7 | SDF | |
| 别名 | N-(6-氯-7-甲氧基-9H-吡啶并[3,4-B]吲哚-8-基)-2-甲基-3-吡啶甲酰胺,ML120B;MLN 120B;MLN-120B | ||
| 化学名 | N-(6-chloro-7-methoxy-9H-pyrido[3,4-b]indol-8-yl)-2-methylpyridine-3-carboxamide | ||
| Canonical SMILES | CC1=C(C=CC=N1)C(=O)NC2=C3C(=CC(=C2OC)Cl)C4=C(N3)C=NC=C4 | ||
| 分子式 | C19H15ClN4O2 | 分子量 | 366.8 |
| 溶解度 | ≥ 13.2 mg/mL in DMSO, ≥ 8.53 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7263 mL | 13.6314 mL | 27.2628 mL |
| 5 mM | 0.5453 mL | 2.7263 mL | 5.4526 mL |
| 10 mM | 0.2726 mL | 1.3631 mL | 2.7263 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet