| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
GR-73632 targets the tachykinin neurokinin 1 (NK1) receptor, a G protein-coupled receptor that is the primary receptor for substance P. The compound is a potent and selective NK1 receptor agonist with an EC50 of 2 nM in guinea pig vas deferens. NK1 receptors are involved in pain transmission, neurogenic inflammation, smooth muscle contraction, and itch signaling. By agonizing NK1 receptors, GR-73632 mimics the effects of substance P, activating downstream signaling pathways including phospholipase C, calcium mobilization, and MAPK activation. The compound shows selectivity for NK1 over other tachykinin receptors.
|
|---|---|
| ln Vitro |
In vitro studies demonstrate that GR-73632 is a potent and selective NK1 receptor agonist with an EC50 of 2 nM. The compound acts directly on the peripheral terminals of primary sensory neurons through the NK1 receptor, which conveys itch signals. GR-73632 promotes differentiation but not survival of rat chromaffin cells in vitro. The compound's potent NK1 agonism makes it a valuable tool for studying NK1 receptor function and substance P signaling. In cellular assays, GR-73632 activates NK1 receptor-mediated signaling pathways.
|
| ln Vivo |
In vivo studies show that GR-73632 can be used in the treatment of asthma and gastrointestinal disorders. As an NK1 receptor agonist, the compound mimics substance P effects on smooth muscle contraction, inflammation, and sensory signaling. The compound's ability to act on peripheral terminals of primary sensory neurons makes it useful for studying itch and pain signaling. Further in vivo studies are warranted to fully characterize the compound's efficacy in various disease models.
|
| Enzyme Assay |
The in vitro receptor binding assay for GR-73632 involves measuring NK1 receptor binding affinity using radioligand binding techniques. Membranes from cells expressing human NK1 receptors are incubated with varying concentrations of GR-73632 (0.01 nM-10 μM) and a fixed concentration of radiolabeled NK1 ligand (e.g., [3H]-substance P). Non-specific binding is determined using excess unlabeled substance P. IC50 values are calculated from competition binding curves. Functional assays measure calcium mobilization using fluorescent indicators (Fluo-4) in NK1 receptor-expressing cells. EC50 values are determined from dose-response curves. Selectivity is confirmed by testing against NK2 and NK3 receptors.
|
| Cell Assay |
In vitro cellular assays for GR-73632 typically use NK1 receptor-expressing cell lines (e.g., CHO, HEK293) or primary neurons. Cells are cultured in appropriate media and treated with the compound at concentrations of 0.01 nM-10 μM for 1-24 hours. Calcium mobilization is measured using fluorescent indicators (Fluo-4, Fura-2). MAPK activation is assessed by Western blot of phosphorylated ERK1/2. Cell differentiation is assessed in rat chromaffin cells by morphological analysis and marker gene expression. Cell viability is assessed using MTT or CCK-8 assays. Receptor internalization is assessed by immunofluorescence.
|
| Animal Protocol |
In vivo animal studies for GR-73632 involve models of asthma, gastrointestinal disorders, pain, and itch. Animals are treated with the compound via intrathecal, intraperitoneal, or intravenous injection at doses of 0.001-10 mg/kg. For asthma models, airway hyperresponsiveness and inflammation are assessed. For gastrointestinal studies, smooth muscle contraction and motility are measured. For itch studies, scratching behavior is quantified. Pain responses are assessed using behavioral tests. Tissue samples are collected for histology and biomarker analysis.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of GR-73632 are not extensively reported. The compound has a molecular weight of 766 and molecular formula of C40H59N7O6S. It is a peptide compound. The compound should be stored at -80°C for long-term preservation and under nitrogen to avoid moisture and light. It is soluble in DMSO and other organic solvents. Based on its peptide nature, the compound may have limited oral bioavailability. Further studies on plasma half-life, clearance, and tissue distribution are needed.
|
| Toxicity/Toxicokinetics |
Toxicological data for GR-73632 is not extensively reported. As an NK1 receptor agonist, the compound may cause effects related to substance P signaling including smooth muscle contraction, inflammation, and pain modulation. The compound is for research use only and not for human therapeutic applications. Standard safety precautions should be followed when handling. For detailed toxicity information, specialized toxicological studies would need to be performed.
|
| References | |
| Additional Infomation |
GR-73632 is a research-grade compound with CAS number 133156-06-6. Its molecular formula is C40H59N7O6S and molecular weight is 766. The compound is a potent and selective NK1 receptor agonist with an EC50 of 2 nM. It acts on peripheral terminals of primary sensory neurons through NK1 receptors, conveying itch signals. It promotes differentiation of rat chromaffin cells and can be used to study asthma and gastrointestinal disorders. This compound has not advanced to clinical trials and is not FDA-approved. It is strictly for research purposes only.
|
| Molecular Formula |
C40H59N7O6S
|
|---|---|
| Molecular Weight |
766.015
|
| Exact Mass |
765.425
|
| CAS # |
133156-06-6
|
| PubChem CID |
119599
|
| Appearance |
White to off-white solid powder
|
| Density |
1.198g/cm3
|
| Boiling Point |
1082.2ºC at 760mmHg
|
| Flash Point |
608.3ºC
|
| Vapour Pressure |
0mmHg at 25°C
|
| Index of Refraction |
1.576
|
| LogP |
4.668
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
22
|
| Heavy Atom Count |
54
|
| Complexity |
1230
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N)N(C)C(=O)[C@@H]1CCCN1C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)CCCCN
|
| InChi Key |
HQKPTSSZOJLFBZ-LJADHVKFSA-N
|
| InChi Code |
InChI=1S/C40H59N7O6S/c1-27(2)24-34(38(51)44-30(36(42)49)20-23-54-4)46(3)40(53)33-18-13-22-47(33)39(52)32(26-29-16-9-6-10-17-29)45-37(50)31(25-28-14-7-5-8-15-28)43-35(48)19-11-12-21-41/h5-10,14-17,27,30-34H,11-13,18-26,41H2,1-4H3,(H2,42,49)(H,43,48)(H,44,51)(H,45,50)/t30-,31-,32-,33-,34-/m0/s1
|
| Chemical Name |
(2S)-N-[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-[(2S)-2-[[(2S)-2-(5-aminopentanoylamino)-3-phenylpropanoyl]amino]-3-phenylpropanoyl]-N-methylpyrrolidine-2-carboxamide
|
| Synonyms |
GR73632. delta-Aminovaleryl-9-pro-10-meleu-substance P (7-10); GR 73632; GR-73632
|
| 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 (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)
|
| Solubility (In Vitro) |
DMSO: ≥ 100 mg/mL (~130.6 mM)
H2O: ~1 mg/mL (~1.3 mM; with ultrasonication) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (3.26 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3054 mL | 6.5272 mL | 13.0545 mL | |
| 5 mM | 0.2611 mL | 1.3054 mL | 2.6109 mL | |
| 10 mM | 0.1305 mL | 0.6527 mL | 1.3054 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
