| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
GRK2 (G protein-coupled receptor kinase 2).
|
|---|---|
| ln Vitro |
CCG258208 (Compound 14as) significantly improved the βAR-stimulated contractility in mouse cardiomyocytes (0–1 μM; 10 min) [1].
GRK2-IN-1 inhibits GRK2 with an IC50 of 30 nM. It shows 230-fold selectivity over GRK5 (IC50 = 7.09 μM) and >2500-fold selectivity over GRK1 (IC50 = 87.3 μM), PKA, and ROCK1. The compound is a potent and selective GRK2 inhibitor suitable for investigating GRK2-mediated signaling in cardiovascular disease. |
| ln Vivo |
Excellent in vivo half-life is demonstrated by treatment with CCG258208 (compound 14as) (ip; 10 mg/kg; once) [1].
No specific in vivo efficacy data are available for GRK2-IN-1 beyond its characterization as a selective GRK2 inhibitor for heart failure research. As a GRK2 inhibitor, it would be expected to restore beta-adrenergic receptor signaling and improve cardiac function in animal models, but specific published in vivo results are not documented. |
| Enzyme Assay |
The kinase assay for GRK2 uses recombinant GRK2 and a synthetic peptide substrate. ATP and the substrate are incubated with the enzyme in the presence of varying concentrations of GRK2-IN-1. Phosphorylation is measured by fluorescence polarization or mass spectrometry. IC50 values are determined from dose-response curves.
|
| Cell Assay |
Cell viability assay [1]
Cell Types: Mouse cardiomyocytes Tested Concentrations: 0, 0.1, 0.5 and 1 μM Incubation Duration: 10 minutes Experimental Results: Significant increase in contractility only at 0.1 μM concentration. In cellular assays, cells expressing beta-adrenergic receptors are treated with GRK2-IN-1. Receptor desensitization is assessed by measuring agonist-induced cAMP accumulation or receptor internalization. GRK2-mediated phosphorylation of the receptor is evaluated by Western blot to confirm target engagement. |
| Animal Protocol |
Animal/Disease Models: CD-1 mice [1]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; 10 mg/kg; primary Experimental Results: demonstrated that the total plasma drug level after a single IP administration exceeded the GRK2 IC50 for seven hrs (hrs (hours)). No specific in vivo animal study protocols are documented for GRK2-IN-1. General heart failure models such as transverse aortic constriction in mice or isoproterenol-induced cardiac dysfunction could be used, with the compound administered systemically, and cardiac function assessed by echocardiography. |
| References |
| Molecular Formula |
C24H26CLFN4O4
|
|---|---|
| Molecular Weight |
488.939048290253
|
| Exact Mass |
452.185
|
| CAS # |
2055990-90-2
|
| Related CAS # |
CCG258208 hydrochloride
|
| PubChem CID |
126476626
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
2.6
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
33
|
| Complexity |
658
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1CNC[C@H]([C@@H]1C2=CC(=C(C=C2)F)C(=O)NCC3=CC=NN3)COC4=CC5=C(C=C4)OCO5
|
| InChi Key |
XQUKEAYUAYTIBV-LPHOPBHVSA-N
|
| InChi Code |
InChI=1S/C24H25FN4O4/c25-21-3-1-15(9-20(21)24(30)27-12-17-5-8-28-29-17)19-6-7-26-11-16(19)13-31-18-2-4-22-23(10-18)33-14-32-22/h1-5,8-10,16,19,26H,6-7,11-14H2,(H,27,30)(H,28,29)/t16-,19-/m0/s1
|
| Chemical Name |
5-[(3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)piperidin-4-yl]-2-fluoro-N-(1H-pyrazol-5-ylmethyl)benzamide
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (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.
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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