| Size | Price | Stock | Qty |
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| Targets |
NF-kappaB inducing kinase (NIK), also known as MAP3K14. NIK is a serine/threonine protein kinase that plays a critical role in the non-canonical NF-kappaB signaling pathway. Activation of NIK leads to phosphorylation and processing of p100 to p52, which then translocates to the nucleus and activates gene expression involved in immune responses, B-cell development, and inflammatory processes. Overactivation of NIK has been implicated in various cancers and autoimmune diseases.
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| ln Vitro |
NIK SMI1 is a potent and selective inhibitor of NIK, suppressing NIK-catalyzed hydrolysis of ATP to ADP with an IC50 of 0.23 +/- 0.17 nM. As a highly selective inhibitor, it specifically targets the ATP-binding site of NIK, blocking its kinase activity and thereby inhibiting the non-canonical NF-kappaB signaling pathway. (S)-NIK SMI1 is the inactive isomer and is used as an experimental control to validate the specificity of observed biological effects.
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| ln Vivo |
No in vivo activity data is provided for (S)-NIK SMI1 itself, as it is intended as an experimental control. The active parent compound NIK SMI1 has been evaluated in preclinical models of hematologic malignancies, including multiple myeloma and diffuse large B-cell lymphoma (DLBCL), where overactivation of non-canonical NF-kappaB signaling is a driver of tumor growth. NIK inhibition leads to reduced tumor growth and enhanced sensitivity to standard-of-care therapies.
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| Enzyme Assay |
For NIK kinase activity assays, a non-cell radioligand binding or ADP-Glo assay is performed. Recombinant human NIK protein is incubated with varying concentrations of the test compound and ATP in assay buffer (40 mM Tris-HCl, pH 7.5, 20 mM MgCl2, 0.1 mg/mL BSA, 50 microM DTT) at 30degC for 30-60 minutes. The reaction is quenched, and ADP production is measured using luminescence-based detection. IC50 values are calculated from dose-response curves using a four-parameter logistic regression. (S)-NIK SMI1 is used as a negative control in these assays.
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| Cell Assay |
A cell-based NF-kappaB reporter assay is performed to assess non-canonical pathway inhibition. HEK293 cells stably transfected with a NF-kappaB luciferase reporter and expressing NIK are seeded in 96-well plates. Cells are treated with serial dilutions of NIK SMI1 (0.01 nM to 10 uM) or the (S)-isomer as control for 6-24 hours. Luciferase activity is measured after adding the substrate, and the reduction in luminescence indicates inhibition of NF-kappaB activation. (S)-NIK SMI1 is used as a negative control to confirm target specificity.
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| Animal Protocol |
For the active parent compound, in vivo efficacy studies are performed in mouse xenograft models of multiple myeloma. Immunodeficient mice are implanted subcutaneously with human multiple myeloma cells. When tumors reach approximately 150-200 mm3, mice are randomized and treated orally with NIK SMI1 at doses of 10-50 mg/kg once or twice daily for 14-28 days. Tumor volumes are measured twice weekly by calipers. At endpoint, tumors are collected for Western blot analysis of p100 processing to p52 (a marker of non-canonical NF-kappaB activation). (S)-NIK SMI1 is used as a negative control in these studies.
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| ADME/Pharmacokinetics |
(S)-NIK SMI1 is soluble in DMSO at 100 mg/mL (273.69 mM). For in vivo administration, the active parent compound NIK SMI1 can be formulated in a vehicle such as 10% DMSO in saline or PEG400/saline. Detailed PK parameters such as half-life, bioavailability, and clearance are not publicly available for this research compound. Storage: Powder -20degC for 3 years; In solvent -80degC for 6 months or -20degC for 1 month.
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| Toxicity/Toxicokinetics |
As an inactive isomer, (S)-NIK SMI1 is non-toxic at the concentrations used for control experiments (typically low uM range). The active NIK SMI1 has been evaluated in preclinical safety studies and is generally well-tolerated at therapeutic doses (10-50 mg/kg) in rodents. NIK inhibitors as a class may have potential effects on immune function due to the role of NIK in B-cell development and inflammatory responses. Comprehensive toxicology data for this research compound is not publicly available.
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| References | |
| Additional Infomation |
(S)-NIK SMI1 is a research-grade chemical used exclusively as a negative control in studies of NF-kappaB inducing kinase (NIK) biology and non-canonical NF-kappaB signaling. The development of NIK inhibitors is an active area of cancer research, particularly for hematologic malignancies such as multiple myeloma and diffuse large B-cell lymphoma (DLBCL), which are dependent on non-canonical NF-kappaB signaling for survival. Key reference: Blaquiere N, et al. Scaffold-Hopping Approach To Discover Potent, Selective, and Efficacious Inhibitors of NF-kappaB Inducing Kinase. J Med Chem. 2018 Aug 9;61(15):6801-6813. This product is for research use only and is not FDA-approved for human therapy.
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| Molecular Formula |
C20H19N3O4
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| Molecular Weight |
365.38
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| Exact Mass |
365.138
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| CAS # |
2984765-48-0
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| Related CAS # |
NIK SMI1;1660114-31-7
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| PubChem CID |
134817169
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| Appearance |
Off-white to pink solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
654
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN1CC[C@@](C1=O)(C#CC2=CC(=CC=C2)C3=NC(=CC(=C3)OC)C(=O)N)O
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| InChi Key |
LQSHXYHWYGKAMX-HXUWFJFHSA-N
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| InChi Code |
InChI=1S/C20H19N3O4/c1-23-9-8-20(26,19(23)25)7-6-13-4-3-5-14(10-13)16-11-15(27-2)12-17(22-16)18(21)24/h3-5,10-12,26H,8-9H2,1-2H3,(H2,21,24)/t20-/m1/s1
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| Chemical Name |
6-[3-[2-[(3S)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-4-methoxypyridine-2-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~100 mg/mL (~273.69 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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