| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Bay 65-1942 HCl is the hydrochloride salt of of BAY65-1942 which is a novel, potent and selective ATP-competitive inhibitor of IKKβ.It targets the IKKbeta kinase activity specifically. Following an acute ischemia-reperfusion injury, IKKbeta inhibition reduces myocardial damage and dysfunction. The CK-MB levels of the animals pretreated with Bay 65-1942 (n=3) were significantly lower than those of the untreated animals before IR (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 |
In order to sufficiently inhibit kinase activity, inhibitors of MEK (AZD6244) and IKK (BAY 65-1942) are used at their IC50 concentrations, as determined by a 48-hour MTS assay. AZD6244 (5 µM), BAY 65-1942 (10 µM), or a combination of these inhibitors at the same concentrations are applied to MYL-R cells for 24 hours. At the dose combination of (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 reports that synergism is present at the IC50 (CI = 0.56±0.09) and IC90 (CI = 0.460.02) dose combinations (CI values are the mean of three independent experiments, ±standard deviation). In comparison to DMSO-treated cells, the effects of AZD6244 and BAY 65-1942 on caspase 3/7 activation are 1.3 and 2 times greater, respectively. Caspase 3/7 activity is 3.2 times higher after treatment with AZD6244 and BAY 65-1942[2].
|
| Cell Assay |
MYL-R cells are plated on a 96-well plate at a density of 4×104 cells/well in a growth medium of 100 µL RPMI containing kinase inhibitors to test the viability of the cells. During the first 24 and second 48 hours, growth media and kinase inhibitors are replenished. Each well is filled with 20 L of the MTS assay reagent. The absorbance at 490 nm is measured after the plate has been in the incubator for roughly an hour. Cells are cultivated and tested for combination index (CI) experiments. Cells are treated with a series of three-fold dilutions of either AZD6244 alone or in combination with BAY 65-1942 (10 µM) while maintaining a constant ratio of 1:2, respectively, to ascertain the dose-effects of each drug. To calculate CI values, cell viability test results are analyzed. Three independent experiments' CI values are averaged[2].
|
| Animal Protocol |
Mice: 8–10 week-old male C57BL/6 mice are used. Mice are given 30 minutes of cardiac ischemia followed by various amounts of reperfusion in order to study the effects of IKK inhibition on myocardial IR injury. At the proper dosing times, Bay 65-1942 (5 mg/kg) is injected intraperitoneally. A 10% cremaphor in water vehicle is given to non-treatment groups. In treatment groups, Bay 65-1942 is administered either before ischemia, during reperfusion, or two hours after reperfusion injury. The size of the infarct is determined 24 hours after the injury caused by the reperfusion in the vehicle, sham, and treatment groups. Serum creatine kinase-muscle-brain fraction (CK-MB) levels are assessed 1 hour after reperfusion in animals that have received Bay 65-1942 treatment in order to confirm myocardial injury.
|
| References |
|
| Additional Infomation |
Bay 65-1942 hydrochloride is an ATP-competitive and selective IKKb inhibitor.
|
| Molecular Formula |
C22H25N3O4.HCL
|
|---|---|
| Molecular Weight |
431.91254
|
| Exact Mass |
431.161
|
| Elemental Analysis |
C, 61.18; H, 6.07; Cl, 8.21; N, 9.73; O, 14.82
|
| CAS # |
600734-06-3
|
| Related CAS # |
758683-21-5 (BAY65-1942 R-isomer); 600734-02-9
|
| PubChem CID |
135454903
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.04
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
30
|
| Complexity |
586
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
O=C1OCC2=C([C@H]3CNCCC3)C=C(C4=C(O)C=CC=C4OCC5CC5)N=C2N1.[H]Cl
|
| InChi Key |
XZTOAEZYOFWVHB-PFEQFJNWSA-N
|
| InChi Code |
InChI=1S/C22H25N3O4.ClH/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);1H/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;hydrochloride
|
| Synonyms |
BAY 65-1942 HCl; BAY-65-1942 hydrochloride; BAY65-1942; BAY 651942; BAY-651942; BAY651942
|
| HS Tariff Code |
2934.99.03.00
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO: ~50 mg/mL (~115.8 mM)
H2O: ~2.2 mg/mL (~5.0 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3153 mL | 11.5765 mL | 23.1530 mL | |
| 5 mM | 0.4631 mL | 2.3153 mL | 4.6306 mL | |
| 10 mM | 0.2315 mL | 1.1576 mL | 2.3153 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
