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BIX 02565

Catalog No.
B1295
RSK2 inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$275.00
In stock
5mg
$238.00
In stock
10mg
$361.00
In stock
25mg
$523.00
In stock
50mg
$855.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

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.

Chemical Properties

StorageStore at -20°C
M.Wt458.56
Cas No.1311367-27-7
FormulaC26H30N6O2
Solubility≥22.95 mg/mL in DMSO; insoluble in H2O; ≥3.17 mg/mL in EtOH with gentle warming and ultrasonic
SDFDownload SDF
Canonical SMILESC[[email protected]](N12)([H])CCNC(C2=CC3=C1C=C(/C(O)=N/C4=NC5=CC=CC=C5N4CCCN(C)C)C=C3)=O
Shipping ConditionEvaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

Protocol

Kinase experiment [1]:

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]:

Animal models

Rats model

Dosage form

1, 3, 10, 30, 100, and 300 mg/kg, p.o. once per day for 4 days

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.

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.

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

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