BMS-066
Based on 1 Customer Validation
BMS-066 is an IKKβ/Tyk2 pseudokinase inhibitor, with IC50s of 9 nM and 72 nM, respectively.
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- Reinheit: 99.09%
- CAS. Nr.: 914946-88-6
- Formel: C19H21N7O2
- Molecular Weight:379.42
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Speicherung:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
- Protokoll
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
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IKKβ 9 nM (IC50) |
Tyk2 72 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| PBMC | IC50 |
150 nM
Compound: 4m, BMS-066
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Antiinflammatory activity in human PBMC assessed as inhibition of LPS-induced TNFalpha release treated for 5 mins before LPS challenge measured after 4 hrs by ELISA
Antiinflammatory activity in human PBMC assessed as inhibition of LPS-induced TNFalpha release treated for 5 mins before LPS challenge measured after 4 hrs by ELISA
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[PMID: 22018461] |
BMS-066 is shown to inhibit IKKβ-catalyzed phosphorylation of IKKβ in vitro with an IC50 of 9 nM and is more than 500-fold selective for IKKβ over the closely related IKKα. To understand the selectivity on a more comprehensive scale, BMS-066 is assayed against 155 additional kinases at 10 μM, and only six of these kinases are inhibited more than 75%. This indicates that BMS-066 is more than 400-fold selective for IKKβ over more than 95% of the kinases tested. For the six kinases showing more than 75% inhibition at 10 μM, IC50 values are determined in dose-response assays and BMS-066 is shown to be more than 30-fold selective against even the next most potently inhibits kinase (Brk). BMS-066 inhibits LPS-stimulated cytokine production in human peripheral blood mononuclear cells, both at the protein and message level, with IC50 values of approximately 200 nM against these endpoints. BMS-066 inhibits the IKKβ-catalyzed phosphorylation of IkBα in LPS stimulated cells with a similar IC50 value[1]. BMS-066 shows IC50 values of 72 and 1020 nM against the Tyk2 pseudokinase domain probe displacement and IL-23-stimulated reporter assays, respectively[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS. Nr. 914946-88-6
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Appearance Solid
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Molecular Weight 379.42
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Formel C19H21N7O2
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Color Off-white to light yellow
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SMILES
CN1C=NC2=C1C(C=C(C3=CC=CC(CNC(COC)=O)=N3)N4)=C4N=C2NC
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Lösungsmittel & Löslichkeit
DMSO : 100 mg/mL (263.56 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.59 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protokoll
When measuring the inhibition by BMS-066 of the phosphorylation of IkBα in human PBMCs, cells at a density of 1×107 per mL in RPMI 1640 medium supplemented with 10% FBS are preincubated for 30 min BMS-066 at 37°C. Cells are then stimulated for 5 min with LPS (100 ng/mL) and pelleted by rapid centrifugation; the pellets are solubilized by use of ice-cold 10×cell lysis buffer. To measure effects on transcription, human PBMCs are plated on 24-well plates at a density of 3×106 cells/well in RPMI 1640 medium plus 10% FBS and HEPES with varying concentrations of BMS-066 (0-10 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Rats, Mice[1]
Male Lewis rats (225 g) are used. Vehicle (0.02 N HCl) or BMS-066 in vehicle is administered by oral gavage beginning on the day of adjuvant challenge. Eight animals are included in each treatment group. Male Lewis rats (250 g) are immunized intraperitoneally with 200 μg/rat of keyhole limpet hemocyanin diluted in phosphate-buffered saline. BMS-066 in 0.02 N HCl is administered by oral gavage once daily beginning on the day of immunization. Blood samples were collected on day 7 and on day 14 under isoflurane anesthesia. Male DBA/1 mice (20-25 g) are immunized with 200 μg/mouse of bovine type II collagen in 0.1 mL at the base of the tail on day 0 and on day 21. Vehicle (0.02 N HCl) or BMS-066 in vehicle is administered by oral gavage twice daily beginning on day 21. Mice were monitored after the second immunization for the development of paw inflammation. Each paw was individually scored as follows: 0, normal; 1, one or more swollen digits; 2, mild paw swelling; 3, moderate paw swelling; 4, fusion of joints/ankylosis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Reinheit & Dokumentation
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Data Sheet (278 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
Verweise
[1]. Gillooly KM, et al. Periodic, partial inhibition of IkappaB Kinase beta-mediated signaling yields therapeutic benefit in preclinical models of rheumatoid arthritis. J Pharmacol Exp Ther. 2009 Nov;331(2):349-60. [Content Brief]
[2]. Tokarski JS, et al. Tyrosine Kinase 2-mediated Signal Transduction in T Lymphocytes Is Blocked by Pharmacological Stabilization of Its Pseudokinase Domain. J Biol Chem. 2015 Apr 24;290(17):11061-74. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.6356 mL | 13.1780 mL | 26.3560 mL | 65.8900 mL |
| 5 mM | 0.5271 mL | 2.6356 mL | 5.2712 mL | 13.1780 mL | |
| 10 mM | 0.2636 mL | 1.3178 mL | 2.6356 mL | 6.5890 mL | |
| 15 mM | 0.1757 mL | 0.8785 mL | 1.7571 mL | 4.3927 mL | |
| 20 mM | 0.1318 mL | 0.6589 mL | 1.3178 mL | 3.2945 mL | |
| 25 mM | 0.1054 mL | 0.5271 mL | 1.0542 mL | 2.6356 mL | |
| 30 mM | 0.0879 mL | 0.4393 mL | 0.8785 mL | 2.1963 mL | |
| 40 mM | 0.0659 mL | 0.3295 mL | 0.6589 mL | 1.6473 mL | |
| 50 mM | 0.0527 mL | 0.2636 mL | 0.5271 mL | 1.3178 mL | |
| 60 mM | 0.0439 mL | 0.2196 mL | 0.4393 mL | 1.0982 mL | |
| 80 mM | 0.0329 mL | 0.1647 mL | 0.3295 mL | 0.8236 mL | |
| 100 mM | 0.0264 mL | 0.1318 mL | 0.2636 mL | 0.6589 mL |
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