NIK SMI1
目录号 : GC31733
NIK SMI1 is a highly potent and selective NF-κB-inducing kinase (NIK) inhibitor with Ki of 0.23 nM for NIK-catalyzed hydrolysis of ATP to ADP.
Cas No.:1660114-31-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Human B cells are re-suspended in RPMI with 10% FBS for the proliferation assays and 2.5% FBS for the survival assays. Mouse B cells are plated in Co-star 96-well plates at either 50,000 cells/well for the survival assays or at 150,000 cells/well for the proliferation assays. Compounds (e.g., NIK SMI1) diluted in DMSO (final DMSO assay concentration=0.1%) are added to the cells. The cells are incubated with NIK SMI1 for one hour at 37°C. Stimulus is then added to the plates and survival or proliferation is measured after four days. For the proliferation assays, cells are treated with either Anti-IgM (20 µg/mL) or rhCD40L (10 µg/mL) or anti-mouse CD40 (100 ng/mL). For the BAFF survival assay, cells are treated with human or mouse rBAFF at 10 ng/mL followed by Cell Titer Glo to measure survival on day four[1]. |
Animal experiment: | Mice[1]Age-matched C57BL/6 mice are used. Only female mice are used in these experiments. The single oral doses of NIK SMI1 are 10, 20, 60, 100, and 200 mg/kg. For PO dosing, animals are manually restrained, then dosed via oral gavage using an appropriately sized gavage needle. Animals are monitored for any signs of aspiration or distress-respiratory abnormalities, lethargy, pale extremities, etc. For sample collection, 3 mice per group are bled a total of 8 times via tail prick using a 27 G needle (lateral tail vein). 10 μL of blood is collected at each timepoint and deposited into a pre-filled costar cluster tube containing 40 μL of 1.7 mg/mL EDTA/water, the tube is capped, votexed for 5 seconds, then stored on dry ice. Samples are transferred to a -80°C freezer for storage[1]. |
References: [1]. Blaquiere N, et al. Scaffold-Hopping Approach To Discover Potent, Selective, and Efficacious Inhibitors of NF-κB Inducing Kinase. J Med Chem. 2018 Aug 9;61(15):6801-6813. | |
NIK SMI1 is a highly potent and selective NF-κB-inducing kinase (NIK) inhibitor with Ki of 0.23 nM for NIK-catalyzed hydrolysis of ATP to ADP.
NIK SMI1 exhibits selective inhibition of LTβR-dependent p52 translocation and transcription of NF-κB2 related genes. NIK SMI1 is shown to have a favorable pharmacokinetic profile across species and to inhibit BAFF-induced B cell survival in vitro.[1]
NIK SMI1 inhibits BAFF signaling and reduces splenic marginal zone B cells in vivo.[1]
[1] Blaquiere N, et al. J Med Chem. 2018 Aug 9;61(15):6801-6813.
| Cas No. | 1660114-31-7 | SDF | |
| Canonical SMILES | O=C(N)C1=NC(C2=CC=CC(C#C[C@]3(O)CCN(C)C3=O)=C2)=CC(OC)=C1 | ||
| 分子式 | C20H19N3O4 | 分子量 | 365.38 |
| 溶解度 | DMSO : 100 mg/mL (273.69 mM) | 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 | 2.7369 mL | 13.6844 mL | 27.3688 mL |
| 5 mM | 0.5474 mL | 2.7369 mL | 5.4738 mL |
| 10 mM | 0.2737 mL | 1.3684 mL | 2.7369 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。
Granulocyte-macrophage colony-stimulating factor suppresses induction of type I interferon in infants with severe pneumonia
Background: The underlying mechanisms for infantile bronchopneumonia development remain unknown.
Methods: Peripheral blood mononuclear cell (PBMCs) and serum derived from severe and mild infantile bronchopneumonia were obtained, and the expression of various molecules was detected with enzyme-linked immunosorbent assay and quantitative PCR. Such molecules were also detected in granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced bone marrow-derived NFκB2-/- dendritic cells (DCs) or NIK SMI1 (NF-κB-inducing kinase inhibitor) administrated DCs.
Results: The relative mRNA expression levels of type I interferons (IFNs) (IFN-α4, IFN-β), Th17 cell-associated markers (interleukin-17A, retinoic-acid-receptor-related orphan nuclear receptor gamma, and GM-CSF), and non-canonical NF-κB member (NFκB2) were significantly up-regulated in PBMCs and DCs derived from infantile bronchopneumonia compared with healthy controls. However, compared with Th17 cell-associated markers and non-canonical NF-κB molecules, the expression of IFN-α4 and IFN-β was significantly inhibited in severe infantile bronchopneumonia compared with mild infantile bronchopneumonia. The relative protein expression of the above molecules also showed a similar expression pattern in the PBMCs or serum. NF-κB2 knockout or NIK SMI1 administration could reverse the diminished expression of IFN-β in GM-CSF-induced bone marrow-derived DCs.
Conclusions: GM-CSF-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in DCs contributes to the development of severe bronchopneumonia in infant.
Impact: Granulocyte-macrophage colony-stimulating factor-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in dendritic cells is critical for the development of infantile bronchopneumonia. Our findings reveal a possible mechanism underlying the development of severe infantile bronchopneumonia. The results could provide therapeutic molecular target for the treatment of such disease.