| Size | Price | |
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| 10mg | ||
| 25mg | ||
| 50mg | ||
| 100mg | ||
| 250mg |
Purity: ≥98%
BMS-066 is a novel and potent tricyclic pseudokinase inhibitors of IKKβ/Tyk2 with IC50s of 9 nM and 72 nM, respectively. It demonstrates potent in vitro potency, acceptable pharmacokinetic and physicochemical properties, and efficacy when dosed orally in a mouse model of inflammatory bowel disease.
| ln Vitro |
BMS-066 is more than 500 times more selective for IKKβ than the closely related IKKα and inhibits IKKβ-catalyzed phosphorylation of IKKβ in vitro with an IC50 of 9 nM. BMS-066 was tested at a concentration of 10 μM against an additional 155 kinases to obtain a more comprehensive understanding of its selectivity; only 6 of them showed better than 75% inhibition. This indicates that BMS-066 exhibits a selectivity of over 400 times for IKKβ when compared to 95% of the tested kinases. For the six kinases that exhibited more than 75% inhibition at 10 μM concentration, IC50 values were ascertained using a dose-response assay; BMS-066 demonstrated more than 30-fold stronger inhibition even when compared to the next most potent inhibitory kinase (Brk) selectivity. BMS-066 has IC50 values of about 200 nM for both protein and message levels, which are the levels at which it inhibits the production of cytokines in human peripheral blood mononuclear cells triggered by lipopolysaccharide (LPS). In LPS-stimulated cells, BMS-066 inhibits IKKβ-catalyzed IkBα phosphorylation with comparable IC50 values [1]. The Tyk2 pseudokinase domain probe replacement and IL-23-stimulated reporter gene tests have IC50 values of 72 and 1020 nM, respectively, for BMS-066 [2].
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| ln Vivo |
At the end of the research, paw swelling was dramatically reduced in rats treated with vehicle compared to rats given oral doses of 5 and 10 mg/kg once daily, beginning at the time of adjuvant injection on Day 1. The high dose demonstrated nearly total suppression of paw swelling. The area of the talocrural (ankle) joint contracts. Within the joint area, inflammatory exudate with neutrophils and cellular debris was also visible. Animals given 10 mg/kg BMS-066 showed normal or barely changed bone resorption and joint inflammation. In addition to dramatically lowering inflammation, low-dose BMS-066 (5 mg/kg) also seems to cause more localized and milder bone resorption as compared to controls. Additionally, dose-dependent protection against substantial pitting, bone loss, woven porous bone, and ossicle fusion was demonstrated by BMS-066 in rats as revealed by hindlimb microcomputed tomography. Measurements of bone density also demonstrated the therapy with BMS-066 to have significant dose-dependent advantages. On the first day of dosing, measurements of serum drug levels in satellite mice revealed that a single dose (dose twice daily, 6 hours per day) covered the IC50 value for LPS-induced TNF-α in mouse whole blood for about 3 hours. Additionally, research has demonstrated that IKKβ inhibitors prevent the tissues in experimental arthritis models from producing TNF-α and IL-1β [1].
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| References |
[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.
[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 |
| Molecular Formula |
C19H21N7O2
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|---|---|
| Molecular Weight |
379.415742635727
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| CAS # |
914946-88-6
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| SMILES |
O(C)CC(NCC1=CC=CC(C2=CC3C(=NC(=C4C=3N(C)C=N4)NC)N2)=N1)=O
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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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6356 mL | 13.1780 mL | 26.3560 mL | |
| 5 mM | 0.5271 mL | 2.6356 mL | 5.2712 mL | |
| 10 mM | 0.2636 mL | 1.3178 mL | 2.6356 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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