CCG258208 (GRK2-IN-1) HCl is a potent and specific inhibitor of GRK2 (G protein-coupled receptor kinase 2) (IC50=30 nM), showing 230-fold activity against GRK5 (IC50=7.09 μM) The selectivity is over 2500-fold for GRK1 (IC50=87.3 μM), PKA and ROCK1. CCG258208 HCl may be utilized in heart failure research.

Physicochemical Properties

Molecular Formula	C24H26CLFN4O4
Molecular Weight	488.94
Related CAS #	CCG258208;2055990-90-2
Appearance	White to off-white solid powder
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	GRK2 30 nM (IC50) GRK5 7.1 μM (IC50)
ln Vitro	Compound 14as, CCG258208(0-1 μM; 10 min), significantly improves mouse cardiomyocytes' βAR-stimulated contractility[1].
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].
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.
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).
References	[1]. Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2Inhibitors Based on Paroxetine. J Med Chem. 2017 Apr 13;60(7):3052-3069.

Solubility Data

Solubility (In Vitro)

DMSO :~250 mg/mL (~511.31 mM) H2O :~50 mg/mL (~102.26 mM)

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. 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. 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 corn oil and mix evenly. 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.  (Please use freshly prepared in vivo formulations for optimal results.)

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.