| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
GRK2 (G protein-coupled receptor kinase 2). CCG258747 is a selective GRK2 inhibitor with high selectivity over GRK1, GRK5, PKA, and ROCK1. It also binds to and blocks the internalization of the micro-opioid receptor.
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| ln Vitro |
CCG258747 inhibits GRK2 with an IC50 of 18 nM, showing high selectivity: 518-fold vs GRK1, 83-fold vs GRK5, >5500-fold vs PKA, and >550-fold vs ROCK1. It also blocks the internalization of the micro-opioid receptor (MOR) without affecting agonist binding affinity. The compound attenuates IgE-mediated anaphylaxis by inhibiting GRK2 and the FcεRI signaling pathway but activates mast cells via MRGPRX2 and MRGPRB2.
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| ln Vivo |
CCG258747 attenuates IgE-mediated anaphylaxis by inhibiting GRK2 and the FcεRI signaling pathway but activates mast cells via MRGPRX2 and MRGPRB2. It can be used to study diseases related to overexpression of GRK2 (such as heart failure, opioid tolerance). Its in vivo efficacy has been evaluated in models of opioid tolerance and cardiac dysfunction, where inhibition of GRK2 restores beta-adrenergic receptor function.
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| Enzyme Assay |
Cell-free GRK2 activity assays are performed using recombinant human GRK2 enzyme. The enzyme is incubated with a peptide substrate (e.g., rhodopsin-derived peptides) and ATP in the presence of increasing concentrations of CCG258747 (0.01-10,000 nM) in assay buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT). The reaction is quenched, and GRK2-mediated substrate phosphorylation is detected by a luminescence-based kinase assay (e.g., ADP-Glo) or by measuring incorporation of 33P from [gamma-33P]-ATP. IC50 is calculated by nonlinear regression. Selectivity is assessed using GRK1, GRK5, PKA, and ROCK1 assays under similar conditions.
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| Cell Assay |
MOR internalization assays: CHO cells or HEK293 cells expressing micro-opioid receptors are pre-incubated with CCG258747 (1-100 microM) for 30-60 min, then stimulated with DAMGO (a micro agonist, 1-10 microM) for 15-60 min. Cells are fixed, permeabilized, and stained with anti-MOR antibody, followed by fluorescent secondary antibody. MOR internalization is quantified by confocal microscopy (plasma membrane vs. cytoplasmic distribution) or by flow cytometry using receptor internalization assays. CCG258747 blocks DAMGO-induced MOR internalization. Mast cell activation: LAD2 human mast cells or mouse peritoneal mast cells are stimulated with IgE/anti-IgE or compound 48/80 (MRGPRX2 agonist) in the presence or absence of CCG258747. Degranulation is measured by beta-hexosaminidase release.
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| Animal Protocol |
For anaphylaxis models: BALB/c mice are sensitized with anti-DNP IgE (i.v.) and then challenged with DNP-HSA (i.v.) 24 h later. CCG258747 is administered i.p. (10-30 mg/kg) 30 min before challenge. Body temperature is measured by rectal probe. Serum histamine and mast cell protease levels are measured by ELISA. For opioid tolerance models: mice are treated with morphine (10 mg/kg, s.c., twice daily for 7 days) with or without CCG258747 (10-30 mg/kg, i.p.). Tolerance is assessed by the tail-flick test. GRK2 levels and MOR phosphorylation in the periaqueductal gray (PAG) are measured by Western blot. For cardiac function models, CCG258747 is administered to mice with pressure overload-induced heart failure. Echocardiography is performed to assess left ventricular function.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data are reported for CCG258747. The molecular weight is 502.54 (C28H27FN4O4). CAS# 2615910-00-2. Purity ≥98%. Storage: -20degC, protected from light. Solubility: DMSO (10-50 mg/mL). The compound is a small molecule and is expected to be orally bioavailable, but oral bioavailability has not been confirmed. Standard PK parameters (t1/2, Cmax, AUC, F%) not reported. The compound can be formulated in 5% DMSO + 95% saline or in PEG400 for in vivo studies.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for CCG258747. In published in vivo studies at doses up to 30 mg/kg, no overt signs of toxicity (weight loss, behavioral changes, or mortality) were reported. However, comprehensive toxicological assessments (hERG, Ames, repeat-dose toxicity) have not been performed. Because CCG258747 blocks MOR internalization, it may modulate opioid analgesic responses but does not appear to be directly toxic. The compound has not entered clinical trials.
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| References | |
| Additional Infomation |
Other information: CCG258747 is a research compound, not FDA-approved. It was originally described as a selective GRK2 inhibitor with an IC50 of 18 nM and is a novel chemical tool for studying GRK2 function in GPCR signaling, heart failure, opioid tolerance, and immune responses. CAS# 2615910-00-2. It is a valuable research tool for investigating the role of GRK2 in cardiac physiology and pathology. For research use only.
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| Molecular Formula |
C28H27FN4O4
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|---|---|
| Molecular Weight |
502.536790132523
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| Exact Mass |
502.201
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| CAS # |
2615910-00-2
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| PubChem CID |
146019255
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
37
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| Complexity |
777
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C(NCC1C2=C(NN=1)C=CC=C2)(=O)C1=CC([C@@H]2CCNC[C@H]2COC2=CC=C3OCOC3=C2)=CC=C1F
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| InChi Key |
KGSBEYKVWODBRD-ICSRJNTNSA-N
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| InChi Code |
InChI=1S/C28H27FN4O4/c29-23-7-5-17(11-22(23)28(34)31-14-25-21-3-1-2-4-24(21)32-33-25)20-9-10-30-13-18(20)15-35-19-6-8-26-27(12-19)37-16-36-26/h1-8,11-12,18,20,30H,9-10,13-16H2,(H,31,34)(H,32,33)/t18-,20-/m0/s1
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| Chemical Name |
5-[(3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)piperidin-4-yl]-2-fluoro-N-(2H-indazol-3-ylmethyl)benzamide
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 100 mg/mL (198.99 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.97 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 25.0 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: 2.5 mg/mL (4.97 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9899 mL | 9.9495 mL | 19.8989 mL | |
| 5 mM | 0.3980 mL | 1.9899 mL | 3.9798 mL | |
| 10 mM | 0.1990 mL | 0.9949 mL | 1.9899 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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