| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
CCG-273220 targets G protein-coupled receptor (GPCR) kinase 5 (GRK5), a member of the GRK family that phosphorylates and desensitizes GPCRs. As a covalent inhibitor, CCG-273220 binds irreversibly to the GRK5 subfamily-specific residue Cys474. This covalent binding results in sustained inhibition of GRK5 activity. The compound is more selective for GRK5 than for GRK2. GRK5 is involved in various physiological processes, and its inhibition has potential therapeutic applications in cardiovascular diseases and cancer.
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| ln Vitro |
Three subfamilies comprise human GRKs (GRK1−GRK7): GRK1 (GRK1 and GRK7), GRK2 (GRK2 and GRK3), and GRK4 (GRK4, GRK5, and GRK6) [1]. CCG273441 (compound 9j) is 1000 times more selective than GRK2 (IC50 = 4.8 μM) but has moderate potency (GRK5 IC50 = 3.8 nM) [1].
In vitro, CCG-273220 is a potent and selective covalent inhibitor of GRK5 with an IC50 of 220 nM. The compound covalently binds to the GRK5 subfamily-specific residue Cys474. Its selectivity for GRK5 over GRK2 makes it a valuable tool for studying GRK5-specific signaling pathways. The compound's covalent binding mechanism provides sustained inhibition, which is advantageous for studying the long-term effects of GRK5 inhibition. CCG-273220 is used in research to study the role of GRK5 in GPCR signaling and disease. |
| ln Vivo |
Specific in vivo activity data for CCG-273220 are not detailed in the available literature. However, as a covalent inhibitor of GRK5, it is being investigated for its potential therapeutic applications. Its in vivo effects would be mediated through the sustained inhibition of GRK5. Further studies in animal models are needed to confirm its in vivo efficacy, pharmacokinetics, and safety. The compound is currently in the research phase.
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| Enzyme Assay |
In vitro enzyme assays for CCG-273220 typically involve measuring the inhibition of GRK5 kinase activity. The kinase is incubated with a peptide substrate and ATP in the presence of varying concentrations of the compound. The incorporation of phosphate into the substrate is measured using a luminescent or radiometric detection system. The IC50 value, representing the concentration required to inhibit 50% of the kinase activity, is calculated from the dose-response curve. The compound's covalent binding can be confirmed by washout experiments, where the compound is removed and the inhibition is maintained. The compound is typically dissolved in DMSO for stock solutions.
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| Cell Assay |
In vitro cell-based assays for CCG-273220 are performed to study its effects on GRK5-mediated signaling in cells. Cells are treated with varying concentrations of the compound for various durations. The phosphorylation of GRK5 substrates is measured by Western blotting. The compound's effects on GPCR signaling pathways can be assessed by measuring downstream signaling events. The covalent nature of the inhibition can be confirmed by washout experiments. The compound is typically dissolved in DMSO and diluted in cell culture medium.
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| Animal Protocol |
Specific in vivo animal experiment protocols for CCG-273220 are not detailed in the available literature. However, as a potential therapeutic agent, it would likely be tested in animal models of cardiovascular diseases or cancer where GRK5 is implicated. The compound could be administered orally, intraperitoneally, or intravenously. The route of administration and dosing would depend on the specific experimental design. The compound's covalent binding mechanism suggests that dosing frequency could be reduced.
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| ADME/Pharmacokinetics |
CCG-273220 has a molecular weight of 494.95 g/mol and the formula C26H24ClFN4O3. The compound appears as a solid powder with a purity of ≥98%. It is a covalent inhibitor of GRK5 with an IC50 of 220 nM. The compound covalently binds the GRK5 subfamily-specific residue Cys474. It is more selective for GRK5 than for GRK2. For storage, the compound is kept at -20°C for up to 3 years or at 4°C for up to 2 years.
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| Toxicity/Toxicokinetics |
Specific toxicological data for CCG-273220 are not provided in the available sources. As a research chemical, its safety profile in humans has not been established. The compound is classified as a research reagent and is not for therapeutic or veterinary use. Standard laboratory safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment. Its purity is typically ≥98%.
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| References | |
| Additional Infomation |
CCG-273220 (CAS 2750414-35-6) is a covalent inhibitor of G protein-coupled receptor (GPCR) kinase 5 (GRK5). It has an IC50 of 220 nM against GRK5. CCG-273220 covalently binds the GRK5 subfamily-specific residue Cys474. The compound is more selective for GRK5 than for GRK2. It has the molecular formula C26H24ClFN4O3 and a molecular weight of 494.95 g/mol. The compound appears as a solid powder. CCG-273220 is intended for research use only.
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| Molecular Formula |
C26H24CLFN4O3
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| Molecular Weight |
494.945168495178
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| Exact Mass |
494.152
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| CAS # |
2750414-35-6
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| PubChem CID |
165412469
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| Appearance |
Yellow to orange solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
847
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClCC(NC1=C(C)NC(/C=C2\C(NC3C=CC(C(N[C@H](C)C4C=CC(=CC=4)F)=O)=CC\2=3)=O)=C1C)=O
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| InChi Key |
IDWBLFLYQVHAFH-LPKQHDGYSA-N
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| InChi Code |
InChI=1S/C26H24ClFN4O3/c1-13-22(29-15(3)24(13)32-23(33)12-27)11-20-19-10-17(6-9-21(19)31-26(20)35)25(34)30-14(2)16-4-7-18(28)8-5-16/h4-11,14,29H,12H2,1-3H3,(H,30,34)(H,31,35)(H,32,33)/b20-11-/t14-/m1/s1
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| Chemical Name |
(3Z)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-N-[(1R)-1-(4-fluorophenyl)ethyl]-2-oxo-1H-indole-5-carboxamide
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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 : ~50 mg/mL (~101.02 mM)
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| 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 | 2.0204 mL | 10.1020 mL | 20.2041 mL | |
| 5 mM | 0.4041 mL | 2.0204 mL | 4.0408 mL | |
| 10 mM | 0.2020 mL | 1.0102 mL | 2.0204 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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