| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
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| Other Sizes |
| Targets |
G protein-coupled receptor kinases (GRKs), potentially including GRK2 and GRK3 isoforms. GRK-IN-1 targets these enzymes, which phosphorylate activated GPCRs, leading to receptor desensitization and internalization.
|
|---|---|
| ln Vitro |
Not reported. As a GRK inhibitor, this compound would enhance GPCR signaling by preventing the phosphorylation and subsequent desensitization of receptors. For example, at the beta2-adrenergic receptor, such inhibition would prolong and amplify the cellular response to an agonist.
|
| Enzyme Assay |
A standard in vitro GRK activity assay is performed using purified GRK enzymes and a substrate, such as light-exposed rhodopsin or a synthetic peptide. The reaction mixture contains [gamma-32P]ATP, the GRK enzyme, the substrate, and varying concentrations of GRK-IN-1. After incubation, the reaction is stopped, and the amount of 32P incorporated into the substrate is measured to determine the compound‘s inhibitory effect.
|
| Cell Assay |
For a cellular desensitization assay, cells expressing a GPCR of interest are pre-incubated with GRK-IN-1 and then stimulated with an agonist. Receptor desensitization is measured by performing a second stimulation with the same agonist and quantifying second messenger production (e.g., cAMP for Gs-coupled receptors). Enhanced second messenger production indicates inhibition of GRK activity.
|
| Animal Protocol |
In vivo pharmacology studies can be performed in rodent models. GRK-IN-1 is administered via intraperitoneal injection. Tissues expressing specific GPCRs (e.g., heart for beta-adrenergic receptors) are collected, and receptor phosphorylation levels are assessed via Western blot using phospho-specific antibodies. Alternatively, cardiac function can be measured via echocardiography after agonist challenge to assess the impact of GRK inhibition on GPCR signaling in vivo.
|
| ADME/Pharmacokinetics |
Not reported. As a research compound, pharmacokinetic properties have not been characterized. As a small molecule, it is expected to have some oral bioavailability, but this would need to be empirically determined. Its molecular weight (363.88) is within the typical range for CNS penetration.
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| Toxicity/Toxicokinetics |
Not reported. The toxicological profile has not been characterized. As a GRK inhibitor, potential on-target toxicity may result from dysregulated GPCR signaling in vital organs. For instance, GRK2 is important in heart failure, so long-term inhibition could have cardiac effects.
|
| Additional Infomation |
N-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-5,6-dimethyl-4-thieno[2,3-d]pyrimidineamine is a benzodioxin and thieno[2,3-d]pyrimidine.
GRKs play a crucial role in GPCR desensitization, a key mechanism of drug tolerance and resistance. GRK-IN-1 is a valuable tool compound for understanding the role of specific GRK isoforms in various GPCR signaling pathways. By inhibiting GRK activity, it can enhance and prolong the effects of GPCR agonists, making it useful in drug discovery for identifying novel therapeutic strategies, such as for treating heart failure (where GRK2 is upregulated) or for enhancing opioid or GLP-1 receptor signaling. |
| Molecular Formula |
C6H10BR3N3
|
|---|---|
| Molecular Weight |
363.88
|
| Exact Mass |
280.916
|
| CAS # |
5423-98-3
|
| PubChem CID |
5253159
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.63g/cm3
|
| Boiling Point |
308ºC at 760mmHg
|
| Flash Point |
140.1ºC
|
| LogP |
2.801
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
23
|
| Complexity |
413
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=C(C)C2=C(NCC3COC4=CC=CC=C4O3)N=CN=C2S1
|
| InChi Key |
WXGIXNLIJQWFLG-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H17N3O2S/c1-10-11(2)23-17-15(10)16(19-9-20-17)18-7-12-8-21-13-5-3-4-6-14(13)22-12/h3-6,9,12H,7-8H2,1-2H3,(H,18,19,20)
|
| Chemical Name |
N-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-5,6-dimethylthieno[2,3-d]pyrimidin-4-amine
|
| 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 | 2.7482 mL | 13.7408 mL | 27.4816 mL | |
| 5 mM | 0.5496 mL | 2.7482 mL | 5.4963 mL | |
| 10 mM | 0.2748 mL | 1.3741 mL | 2.7482 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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