BIX 02565 |
| Catalog No.GC12982 |
BIX 02565 est un puissant inhibiteur de la ribosome S6 kinase 2 (RSK2) avec une IC50 de 1,1 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1311367-27-7
Sample solution is provided at 25 µL, 10mM.
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BIX 02565 is a novel inhibitor of ribosomal S6 kinase 2 with IC50 value of 1 nM [1].
Ribosomal S6 kinase (RSK) is a Na/H exchanger (NHE) -activating factor and is important for pH maintenance during the early phase of cellular stress. While, NHE activation leads to Ca2+ overload and cardiac hypertrophy over longer periods [2].
BIX 02565 is a novel RSK2 inhibitor. Also, BIX 02565 inhibited adrenergic ɑ1A-, ɑ1B-, ɑ1D-, ɑ2A-, β2- and imidazoline I2 receptors with IC50 values ranging from 0.052 to 1.820 μM. These receptors played important roles in the regulation of vascular tone and cardiac function [2]. Also, BIX 02565 inhibited LRRK2 and PRKD1 with IC50 values of 16 and 35 nM [1].
In the rat CV screen, BIX 02565 (1, 3 and 10 mg/kg) significantly decreased heart rate (-93 +13 beats/min) and mean arterial pressure (MAP: to -65 +6 mm Hg below baseline). In telemetry-instrumented rats, BIX 02565 (30, 100 and 300 mg/kg for 4 days) reduced MAP (to -39 + 4 mm Hg) in a concentration-dependent way [2].
References:
[1]. Kirrane TM, Boyer SJ, Burke J, et al. Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity. Bioorg Med Chem Lett, 2012, 22(1): 738-742.
[2]. Fryer RM, Muthukumarana A, Chen RR, et al. Mitigation of off-target adrenergic binding and effects on cardiovascular function in the discovery of novel ribosomal S6 kinase 2 inhibitors. J Pharmacol Exp Ther, 2012, 340(3): 492-500.
| Kinase experiment [1]: | |
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Determination of IC50 at RSK2 |
Compounds were assessed for their ability to inhibit the phosphorylation of a substrate peptide by RSK2 as described previously (Boyer et al., 2011). In brief, human RSK2 protein (Invitrogen, Carlsbad, CA) was used to measure kinase activity utilizing Kinase GloPlus (Promega, Madison, WI) that uses a luciferin-luciferase based detection reagent to quantify residual ATP. The relative light unit signal was measured on an LJL Analyst (Molecular Devices, Sunnyvale, CA) in luminescence mode using 384 aperture; relative light unit signals were converted to percentage of control; the IC50 was fitted to a standard four-parameter logistic equation. |
| Animal experiment [1]: | |
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Animal models |
Rats model |
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Dosage form |
1, 3, 10, 30, 100, and 300 mg/kg, p.o. once per day for 4 days |
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Applications |
BIX 02565 (1, 3, and 10 mg/kg) elicited decreases in both mean arterial pressure and heart rate in anesthetized rats. Moreover, BIX 02565 (30, 100, and 300 mg/kg) also induced concentration-dependent decreases in mean arterial pressure (MAP) after each daily oral dose in telemetry-instrumented conscious rats. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Fryer, R. M., Muthukumarana, A., Chen, R. R., Smith, J. D., Mazurek, S. N., Harrington, K. E., Dinallo, R. M., Burke, J., DiCapua, F. M., Guo, X., Kirrane, T. M., Snow, R. J., Zhang, Y., Soleymanzadeh, F., Madwed, J. B., Kashem, M. A., Kugler, S. Z., O'Neill, M. M., Harrison, P. C., Reinhart, G. A. and Boyer, S. J. (2012) Mitigation of off-target adrenergic binding and effects on cardiovascular function in the discovery of novel ribosomal S6 kinase 2 inhibitors. J Pharmacol Exp Ther. 340, 492-500 | |
| Cas No. | 1311367-27-7 | SDF | |
| Canonical SMILES | C[C@](N12)([H])CCNC(C2=CC3=C1C=C(/C(O)=N/C4=NC5=CC=CC=C5N4CCCN(C)C)C=C3)=O | ||
| Formula | C26H30N6O2 | M.Wt | 458.56 |
| Solubility | ≥ 22.95mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1807 mL | 10.9037 mL | 21.8074 mL |
| 5 mM | 0.4361 mL | 2.1807 mL | 4.3615 mL |
| 10 mM | 0.2181 mL | 1.0904 mL | 2.1807 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 32 reference(s) in Google Scholar.)
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