| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
GRK2 30 nM (IC50) GRK5 7.1 μM (IC50)
CCG258208 hydrochloride selectively targets G protein-coupled receptor kinase 2 (GRK2) with an IC50 of 30 nM. It shows 230-fold selectivity over GRK5 (IC50 = 7.09 microM) and over 2500-fold selectivity over GRK1 (IC50 = 87.3 microM), PKA, and ROCK1. It is a derivative of paroxetine with improved potency and selectivity. |
|---|---|
| ln Vitro |
Compound 14as, CCG258208(0-1 μM; 10 min), significantly improves mouse cardiomyocytes' βAR-stimulated contractility[1].
In vitro, CCG258208 (0-1 microM; 10 minutes) significantly improves beta-adrenergic receptor (betaAR)-stimulated contractility in mouse cardiomyocytes. It exhibits a 100-fold improvement in cardiomyocyte contractility assays compared to paroxetine, demonstrating its enhanced potency as a GRK2 inhibitor in functional cellular assays. |
| ln Vivo |
In vivo, CCG258208 (Compound 14as) therapy exhibits a superior half-life when administered intraperitoneally at a dose of 10 mg/kg once[1].
In vivo, CCG258208 (10 mg/kg; intraperitoneal injection; once) exhibits a superior half-life and robust therapeutic effects in multiple animal models of heart failure, including post-myocardial infarction (MI) models. At 100-fold lower doses than paroxetine, it shows 50-fold higher selectivity for GRK2 and improves cardiac function. |
| Enzyme Assay |
For in vitro enzyme inhibition assays, purified recombinant GRK2 is incubated with a substrate (e.g., rhodopsin or a peptide) and gamma-33P-ATP in reaction buffer with varying concentrations of CCG258208 hydrochloride (0-100 microM). The reaction is stopped, and phosphorylated substrate is quantified by scintillation counting. IC50 is calculated by fitting data to a dose-response curve.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: Mouse cardiomyocytes Tested Concentrations: 0, 0.1, 0.5, and 1 μM Incubation Duration: 10 min Experimental Results: demonstrated a significant increase in contractility at a concentration of only 0.1 μM. For cell-based assays, adult mouse ventricular cardiomyocytes are isolated and plated on laminin-coated coverslips. Cells are treated with CCG258208 (0, 0.1, 0.5, and 1 microM) for 10 minutes. Contractility is measured using a video edge-detection system or IonOptix system to monitor sarcomere shortening and relengthening in response to electrical stimulation. |
| Animal Protocol |
Animal/Disease Models: CD-1 mice[1]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip)injection; 10 mg/kg; once Experimental Results: demonstrated total plasma drug levels after single IP administration that exceed the GRK2 IC50 for seven hrs (hours). For in vivo studies, mouse models of heart failure are used, including a coronary artery ligation model of MI in male C57BL/6 mice (8-10 weeks). CCG258208 is administered daily via intraperitoneal injection (10 mg/kg). Cardiac function is assessed by echocardiography at baseline and weekly thereafter for 4-8 weeks. |
| ADME/Pharmacokinetics |
In CD-1 mice, CCG258208 hydrochloride (10 mg/kg; intraperitoneal injection; once) demonstrates a superior half-life, with total plasma drug levels exceeding the GRK2 IC50 for seven hours. The hydrochloride salt enhances aqueous solubility and potentially improves formulation properties. Its half-life supports once-daily dosing in animal studies.
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| Toxicity/Toxicokinetics |
In preclinical studies, CCG258208 demonstrated a favorable safety profile. No significant changes in survival rate or overt signs of toxicity were observed in animal models of heart failure at therapeutic doses. It shows high selectivity for GRK2, which may minimize off-target effects on other GRKs or kinases at therapeutic concentrations.
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| References | |
| Additional Infomation |
CCG258208 hydrochloride (GRK2-IN-1 hydrochloride) is a research-grade compound derived from the paroxetine scaffold, with a 100-fold improvement in potency over paroxetine in cardiac contractility assays. It is provided as a hydrochloride salt to improve solubility and stability. This compound is not approved for human use.
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| Molecular Formula |
C24H26CLFN4O4
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|---|---|
| Molecular Weight |
488.94
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| Related CAS # |
CCG258208;2055990-90-2
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| Appearance |
White to off-white solid powder
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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 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)
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| Solubility (In Vitro) |
DMSO :~250 mg/mL (~511.31 mM)
H2O :~50 mg/mL (~102.26 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.25 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 20.8 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: ≥ 2.08 mg/mL (4.25 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 20.8 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: ≥ 2.08 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (102.26 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0452 mL | 10.2262 mL | 20.4524 mL | |
| 5 mM | 0.4090 mL | 2.0452 mL | 4.0905 mL | |
| 10 mM | 0.2045 mL | 1.0226 mL | 2.0452 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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