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5mg |
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Purity: ≥98%
TBK1/IKKε-IN-1 is a novel, potent dual TBK1 and IKKε inhibitor with potential anticancer activity. TBK1 (TANK-binding kinase 1) is a noncanonical IκB protein kinase, mediates NF-κB activation in cancer by phosphorylating and activating downstream targets like IRF3 and c-Rel. KRAS-mutant non-small cell lung cancer (NSCLC) has been shown in prior studies to be synthetically lethal when TBK1 is present; as a result, TBK1 may represent a new target for treatment of NSCLC.
Targets |
TBK1 (IC50 = 0.6 nM); IKKε (IC50 = 3.9 nM)
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ln Vitro |
In the Ulight kinase assay, TBK1/IKKε-IN-2 (Cmpound #1) inhibits TBK1 biochemical function with IC50 values of 0.6 and 2.6 nM, respectively, at ATP concentrations of 5 and 250 μM. With an IC50 of 3.9 nM and 10 μM ATP, TBK1/IKKε-IN-2 inhibits the biochemical activity of IKK in the Ulight kinase assay. The Panc 02.13 proliferation assay measures TBK1/IKKε-IN-2 at an IC50 of 5 μM[1].
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ln Vivo |
Experiments on cell proliferation are conducted in a 96-well format (6 replicates), Panc 02.At a density of 2,000 to 5,000 cells per well, 13 cells are plated. At 24 hours after cell seeding, the cells are treated with tool inhibitor titrations (e.g., TBK1/IKKε-IN-2, 1 nM, 10 nM, 100 nM, 1 μM and 10 μM) for 4 days at 37°C before being assessed using the ATP CellTiter-Glo luminescent cell viability assay[1].
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Cell Assay |
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References |
Molecular Formula |
C26H27N5O3
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Molecular Weight |
457.5243
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Exact Mass |
457.21138974
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CAS # |
1292310-49-6
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Related CAS # |
1292310-49-6
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Appearance |
Solid powder
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SMILES |
C1COCCC1OC2=C(C=C(C=C2)C3=NC(=NC=C3)NC4=CC=C(C=C4)N5CCOCC5)C#N
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InChi Key |
BWABTWGSXHTHCG-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C26H27N5O3/c27-18-20-17-19(1-6-25(20)34-23-8-13-32-14-9-23)24-7-10-28-26(30-24)29-21-2-4-22(5-3-21)31-11-15-33-16-12-31/h1-7,10,17,23H,8-9,11-16H2,(H,28,29,30)
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Chemical Name |
5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-2-(oxan-4-yloxy)benzonitrile
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Synonyms |
IKKε-IN-1; MDK10496; MDK10496; MDK10496
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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: 21.5~60 mg/mL (47~131.1 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 | 2.1857 mL | 10.9285 mL | 21.8570 mL | |
5 mM | 0.4371 mL | 2.1857 mL | 4.3714 mL | |
10 mM | 0.2186 mL | 1.0928 mL | 2.1857 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.
KRAS-mutant NSCLC cell lines showed variable sensitivity and dependency to the knockdown of TBK1. Mol Cancer Res . 2014 Jul;12(7):1055-66. td> |
pIRF3S386 is elevated in pancreatic cancer cell lines and is a biomarker of TBK1 activity. Mol Cancer Res . 2014 Jul;12(7):1055-66. td> |
TBK1 inhibitors reduced endogenous p-IRF3S386 in Panc 02.13 cells. Mol Cancer Res . 2014 Jul;12(7):1055-66. td> |
Multiple TBK1 kinase inhibitors showed only modest activity in three different cancer cell line panels. Mol Cancer Res . 2014 Jul;12(7):1055-66. td> |
Rescue experiment using an engineered H23-TBK1-WT overexpression cell line and the 3′UTR-targeting shRNA-T17. Mol Cancer Res . 2014 Jul;12(7):1055-66. td> |