| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
RSK2 (IC50 = 1.1 nM)
BIX 02565 targets ribosomal S6 kinase 2 (RSK2), a member of the MAPK/ERK signaling pathway that plays a role in cell proliferation, survival, and differentiation. It is a potent RSK2 inhibitor with an IC50 of 1.1 nM. BIX 02565 also demonstrates significant off-target binding at multiple adrenergic receptor subtypes that are important for vascular tone and cardiac function, including α1A, α1B, α1D, α2A, β2, and imidazoline I2 receptors, with IC50 values ranging from 0.052 to 1.820 μM. This multi-target profile is relevant for its cardiovascular effects. |
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| ln Vitro |
BIX 02565 is a potent RSK2 inhibitor that, through indirect NHE inhibition, targets the treatment of heart failure secondary to myocardial infarction[1]. Its IC50 value is 1.1 nM. A second Rsk inhibitor, BIX 02565, guards against the reaction of biotinylated nucleotide acyl phosphates with enzyme active sites[2].
In vitro, BIX 02565 is a potent RSK2 inhibitor with an IC50 of 1.1 nM. It protects enzyme active sites from reaction with biotinylated nucleotide acyl phosphates. The compound shows off-target binding at adrenergic receptor subtypes with IC50 values ranging from 0.052 to 1.820 μM. In ex vivo studies, BIX 02565 produces concentration-dependent relaxation in phenylephrine-constricted rat aortic rings at concentrations above 0.03 μM, with a calculated EC50 of 3.1 μM. This vasorelaxant activity is attributed to its adrenergic receptor binding. |
| ln Vivo |
BIX 02565 causes concentration-dependent drops in MAP after each dose in telemetry-equipped rats (30, 100, and 300 mg/kg p.o. QD for 4 days), reaching -39±4 Hg at Tmax on day 4. At concentrations above 0.03 μM and an estimated EC50 of 3.1 μM, BIX 02565 causes concentration-dependent relaxation ex vivo in the phenylephrine-constricted rat aortic ring. The effect of the drug on hemodynamics is then tested in vivo by administering BIX 02565 to anesthetized rats in a low-dose (0.1, 0.3, and 1.0 mg/kg per 20 min) and high-dose (1.0, 3.0, and 10.0 mg/kg per 20 min) series of continuous infusions[1].
In vivo, BIX 02565 has been studied in telemetry-instrumented rats at oral doses of 30, 100, and 300 mg/kg QD for 4 days. It elicits concentration-dependent decreases in mean arterial pressure (MAP) after each dose, reaching -39±4 mm Hg on day 4 at Tmax. The compound also produces concentration-dependent relaxation ex vivo in rat aortic rings. In anesthetized rats, BIX 02565 was infused in low-dose (0.1-1.0 mg/kg per 20 min) and high-dose (1.0-10.0 mg/kg per 20 min) series to test its effects on hemodynamics. These studies confirm the compound's cardiovascular activity. |
| Enzyme Assay |
In vitro enzyme assays for BIX 02565 measure its inhibition of RSK2 kinase activity. Kinase assays are performed using recombinant RSK2, a peptide substrate, and ATP in the presence of varying concentrations of BIX 02565. The incorporation of phosphate into the substrate is measured, and the IC50 is determined from the dose-response curve. Radioligand binding studies are performed to assess the compound's affinity for adrenergic receptor subtypes. Mean percentage inhibition of specific binding is measured, and IC50 values are determined when inhibition exceeds 50%.
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| Cell Assay |
MDS Pharma Services conducts radioligand binding studies. In selected assays (for BIX 02565) where inhibition of adrenergic binding generally exceeded 50%, an IC50 is determined by a nonlinear least-squares regression analysis. The mean percentage inhibition of specific binding or activity is shown for each assay tested. Briefly, Kinase GloPlus measures kinase activity using human RSK2 protein and quantifies residual ATP using a luciferin-luciferase-based detection reagent. The relative light unit signal is measured on an LJL Analyst in luminescence mode with a 384 aperture; relative light unit signals are converted to percentage of control; and the IC50 is fitted to a conventional four-parameter logistic equation[1].
In vitro cell-based assays for BIX 02565 are used to study its effects on RSK2 signaling and adrenergic receptor function. Cells expressing RSK2 are treated with BIX 02565, and the phosphorylation of RSK2 substrates is measured by Western blotting. For adrenergic receptor studies, cells expressing specific receptor subtypes (e.g., α1A, β2) are treated with BIX 02565, and downstream signaling such as calcium mobilization or cAMP accumulation is measured. The compound's ability to induce vasorelaxation can be studied using isolated rat aortic ring preparations. |
| Animal Protocol |
Rats: Male Sprague-Dawley rats (n=6) equipped with telemetry transmitters and conscious and mobile are used to measure mean arterial pressure. BIX 02565 is administered as a solution (10 mL/kg) in a 20% hydroxy-propyl-β-cyclodextran vehicle (30, 100, and 300 mg/kg p.o. QD). The compound is given at 0, 24, 48, and 72 hours; mean arterial pressure is recorded starting at 2 hours before (baseline) and continuing for 90 hours after the first dose. In order to perform a mass spectrometric analysis of the plasma drug concentrations on days 1 and 4, blood is drawn from satellite rats (n=3/group) at 1 hour after the dose (Tmax).
In vivo animal experiments for BIX 02565 are conducted in rat models to study its cardiovascular effects. In telemetry-instrumented rats, BIX 02565 is administered orally at doses of 30, 100, and 300 mg/kg QD for 4 days, and mean arterial pressure is monitored. In anesthetized rats, the compound is infused intravenously in low-dose and high-dose series to assess hemodynamic effects. Ex vivo studies use phenylephrine-constricted rat aortic rings to measure concentration-dependent relaxation. These studies provide evidence for the compound's in vivo cardiovascular activity. |
| ADME/Pharmacokinetics |
BIX 02565 has a molecular weight of 458.56 g/mol and a molecular formula of C26H30N6O2. It is a solid powder with a purity of ≥98%. It is soluble in DMSO at 20.75 mg/mL (45.25 mM) with ultrasonic warming. For in vivo administration, it can be formulated in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline or 10% DMSO + 90% corn oil. For storage, it is recommended to keep the powder at -20°C for up to 3 years or at 4°C for up to 2 years. In solvent, it can be stored at -80°C for 2 years or at -20°C for 1 year.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for BIX 02565 is not provided in standard product descriptions. In vivo studies have used oral doses up to 300 mg/kg in rats without reported overt toxicity. However, comprehensive toxicological studies have not been reported. As a compound with adrenergic receptor activity, it may have cardiovascular effects at higher doses. As with all research chemicals, standard laboratory safety precautions should be followed when handling BIX 02565. Its use is limited to research applications and it is not intended for human or veterinary use.
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| References |
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| Additional Infomation |
BIX 02565 is a research compound and is not approved for any clinical or therapeutic use. It is a potent RSK2 inhibitor with an IC50 of 1.1 nM. BIX 02565 also demonstrates off-target binding at multiple adrenergic receptor subtypes that are important for vascular tone and cardiac function. The compound has been studied as a potential treatment for heart failure secondary to myocardial infarction through indirect NHE inhibition. Its mechanism of action involves inhibiting RSK2 and modulating adrenergic receptor signaling. BIX 02565 is a valuable research tool for studying RSK2 and adrenergic receptor pharmacology.
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| Molecular Formula |
C26H30N6O2
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|---|---|
| Molecular Weight |
458.57
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| Exact Mass |
458.243
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| Elemental Analysis |
C, 68.10; H, 6.59; N, 18.33; O, 6.98
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| CAS # |
1311367-27-7
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| Related CAS # |
1311367-27-7
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| PubChem CID |
53246941
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| Appearance |
White to light yellow solid powder
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| LogP |
4.291
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
747
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C(C1=CC2=C(C=C1)C=C3N2[C@H](C)CCNC3=O)NC4=NC5=CC=CC=C5N4CCCN(C)C
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| InChi Key |
ZHMXXVNQAFCXKK-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C26H30N6O2/c1-17-11-12-27-25(34)23-15-18-9-10-19(16-22(18)32(17)23)24(33)29-26-28-20-7-4-5-8-21(20)31(26)14-6-13-30(2)3/h4-5,7-10,15-17H,6,11-14H2,1-3H3,(H,27,34)(H,28,29,33)/t17-/m1/s1
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| Chemical Name |
(5R)-N-[1-[3-(dimethylamino)propyl]benzimidazol-2-yl]-5-methyl-1-oxo-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indole-8-carboxamide
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| Synonyms |
BIX-02565; BIX02565;BIX 02565
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| HS Tariff Code |
2934.99.9001
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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 Vitro) |
DMSO: ~20.8 mg/mL (~45.3 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (3.64 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 16.7 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: ≥ 1.67 mg/mL (3.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1807 mL | 10.9035 mL | 21.8069 mL | |
| 5 mM | 0.4361 mL | 2.1807 mL | 4.3614 mL | |
| 10 mM | 0.2181 mL | 1.0903 mL | 2.1807 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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