| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
BAY65-1942 is a novel, potent and selective ATP-competitive inhibitor of IKKβ. IKKβ kinase activity is a specific target. Inflammation caused by acute ischemia-reperfusion injury is reduced by IKKbeta inhibition. Comparing animals pretreated with Bay 65-1942 (n=3) to those not treated before IR, the difference in CK-MB levels was significant 14,170 ±3,219 units, P<0.05 vs. vehicle).
| Targets |
IKKβ
|
|---|---|
| ln Vitro |
Compared to animals receiving a vehicle, the size of the left ventricular infarct is significantly reduced when Bay 65-1942 is administered before ischemia. Animals receiving vehicles have a significantly higher infarct-to-area at risk (AAR) ratio than sham animals (70.7±3.4 vs. 5.8±3.4%, P<0.05). Treatment with Bay 65-1942 at each time point significantly lowers this ratio (prior to ischemia 42.7±4.1%, at reperfusion 42.7±7.5%, 2 hours after reperfusion 29.4±5.2%; each group P<0.05 vs. vehicle). The CK-MB levels in the animals pretreated with Bay 65-1942 (n=3) were significantly lower than those in the control group before IR (14,170 ±3,219 units, P<0.05 vs. vehicle)[1].
|
| ln Vivo |
Utilizing inhibitors of MEK (AZD6244) and IKK (BAY 65-1942) at their IC50 concentrations, as determined by a 48-hour MTS assay, is sufficient for inhibiting kinase activity. AZD6244 (5 µM), BAY 65-1942 (10 µM), or a mixture of these inhibitors at the same concentrations are applied to MYL-R cells for 24 hours. At the dose combination (5 µM AZD6244+10 µM BAY 65-1942), which correlates with IC75 (CI = 0.48±0.01), AZD6244 and BAY 65-1942 show synergistic inhibition of cell viability. Additionally, the software's reported IC50 (CI = 0.56±0.09) and IC90 (CI = 0.46±0.02) dose combinations show synergism (CI values are the mean of three independent experiments, standard deviation). Comparing treated cells with DMSO and those treated with AZD6244 and BAY 65-1942, the activation of caspase 3/7 is increased by 2 and 1.3 times, respectively. Caspase 3/7 activity is increased 3.2-fold when AZD6244 and BAY 65-1942 are administered together[2].
|
| Cell Assay |
The viability of the cells is assessed by seeding 4×104 MYL-R cells per well in a 96-well plate with 100 µL of RPMI growth medium that has been enhanced with kinase inhibitors. At 24 and 48 hours, growth media and kinase inhibitors are replaced. Each well receives 20 µL of MTS assay reagent. The plate is put back in the incubator for about an hour, after which the absorbance at 490 nm is measured. Cells are grown and assessed for combination index (CI) experiments. Cells are treated with a series of three-fold dilutions of either AZD6244 or BAY 65-1942 (10 µM) alone or in combination while keeping a constant ratio of 1:2, as appropriate, in order to study the dose-effects of each drug. To determine CI values, cell viability test results are examined. The average of three separate experiments' CI values is used[2].
|
| Animal Protocol |
Mice: Mice are given 30 minutes of cardiac ischemia followed by different lengths of reperfusion to study the effects of IKKβ inhibition on myocardial IR injury. At the proper dosing intervals, a 5-mg/kg intraperitoneal injection of Bay 65-1942 is given. Non-treatment groups are given a 10% cremaphor in water vehicle. Depending on the treatment group, Bay 65-1942 is administered either before ischemia, during reperfusion, or two hours after reperfusion injury. Infarct size in the sham, vehicle, and each treatment group is assessed 24 hours after reperfusion injury. In animals pretreated with Bay 65-1942, serum creatine kinase-muscle-brain fraction (CK-MB) levels are assessed 1 hour after reperfusion to confirm myocardial injury.
|
| References |
|
| Molecular Formula |
C22H25N3O4
|
|---|---|
| Molecular Weight |
395.4516
|
| Exact Mass |
395.185
|
| Elemental Analysis |
C, 66.82; H, 6.37; N, 10.63; O, 16.18
|
| CAS # |
600734-02-9
|
| Related CAS # |
600734-06-3 (HCl salt); 758683-21-5 (BAY65-1942 R-isomer)
|
| PubChem CID |
135454904
|
| Appearance |
Solid powder
|
| Density |
1.286g/cm3
|
| LogP |
4.238
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
29
|
| Complexity |
586
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
O=C1OCC2=C([C@H]3CNCCC3)C=C(C4=C(O)C=CC=C4OCC5CC5)N=C2N1
|
| InChi Key |
IGJVFGZEWDGDOO-CQSZACIVSA-N
|
| InChi Code |
InChI=1S/C22H25N3O4/c26-18-4-1-5-19(28-11-13-6-7-13)20(18)17-9-15(14-3-2-8-23-10-14)16-12-29-22(27)25-21(16)24-17/h1,4-5,9,13-14,23,26H,2-3,6-8,10-12H2,(H,24,25,27)/t14-/m1/s1
|
| Chemical Name |
7-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-5-[(3S)-piperidin-3-yl]-1,4-dihydropyrido[2,3-d][1,3]oxazin-2-one
|
| Synonyms |
BAY65-1942 free base; BAY 65-1942; BAY-65-1942; BAY65-1942; BAY 651942; BAY-651942; BAY651942
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.5288 mL | 12.6438 mL | 25.2876 mL | |
| 5 mM | 0.5058 mL | 2.5288 mL | 5.0575 mL | |
| 10 mM | 0.2529 mL | 1.2644 mL | 2.5288 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA