| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
GR-46611 targets the 5-HT1D receptor, a serotonin (5-hydroxytryptamine) receptor subtype that is a G protein-coupled receptor. 5-HT1D receptors are expressed in the central nervous system and peripheral tissues and are involved in regulating neurotransmitter release, vasoconstriction, and other physiological processes. By acting as a 5-HT1D receptor agonist, GR-46611 activates downstream signaling pathways mediated by Gi/o proteins, leading to inhibition of adenylyl cyclase and modulation of neuronal excitability.
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| ln Vitro |
CEM cell proliferation is induced by GR-46611 (1 μM, 48 hours) [2].
In vitro, GR-46611 acts as a 5-HT1D receptor agonist. It has been used to study 5-HT1D receptor pharmacology and signaling. The compound's activity at 5-HT1D receptors has been characterized in radioligand binding and functional assays. It has potential applications in studying bladder hyperactivity and leukemia. The compound may also have effects on inflammation and neuroprotection, though further studies are needed to fully characterize its cellular activities. |
| ln Vivo |
GR-46611 (1 mg/kg, intraperitoneal injection) significantly improves the survival rate of Dravet syndrome (DS) mice [1]. GR-46611 (0.03-300 μg/kg, intravenously) increases threshold capacity, bladder capacity, and residual capacity in cats with chronic spinal cord injury (SCI) [3]. GR46611 (3-30 mg/kg, subcutaneous injection) causes a dose-related decrease in rectal temperature in adult guinea pigs [4].
In vivo, GR-46611 has been used in guinea pig models to study centrally acting 5-HT1D receptor ligands. Blockade of GR-46611-induced hypothermia provides a useful model for studying the potency and duration of action of 5-HT1D receptor ligands. The compound has potential applications in studying neurological disorders such as Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. However, specific efficacy data in these disease models have not been detailed. |
| Enzyme Assay |
For receptor binding assays, membrane preparations from cells expressing human 5-HT1D receptors are incubated with radiolabeled ligands (such as [³H]5-HT or [³H]GR-125743) at various concentrations of GR-46611 (typically 0.001-10 µM) in binding buffer. Nonspecific binding is determined in the presence of excess unlabeled ligand. Bound radioligand is separated by filtration and radioactivity is quantified by scintillation counting. Ki values are calculated from competition binding curves.
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| Cell Assay |
Cell proliferation assay [2]
Cell Types: CEM cells (human T lymphocytic leukemia cell line) Tested Concentrations: 1 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induced cell proliferation Dramatically increased by 37.0%. For functional assays, cells expressing 5-HT1D receptors are used to measure receptor activation. GR-46611 is added at various concentrations, and downstream signaling is measured, such as inhibition of forskolin-stimulated cAMP accumulation using a cAMP ELISA or HTRF assay. EC50 values for receptor activation are calculated from dose-response curves. The compound's efficacy as a full or partial agonist can be determined by comparing its maximal response to that of a reference agonist such as 5-HT. |
| Animal Protocol |
Animal/Disease Models: Dravet Syndrome (DS) Mice [1] Doses: 0.01, 0.1 and 1 mg/kg
Route of Administration: intraperitoneal (ip) injection Experimental Results: Improved survival and increased survival relative to vehicle-treated controls 89%. For in vivo studies, guinea pigs are administered GR-46611 via appropriate routes, and body temperature is monitored to assess 5-HT1D receptor-mediated hypothermia. Antagonists can be co-administered to study the blockade of GR-46611-induced effects, providing a model for evaluating centrally acting 5-HT1D receptor ligands. For disease models, appropriate animal models of bladder hyperactivity, leukemia, or neurodegeneration would be used to evaluate the compound's therapeutic potential. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of GR-46611 have not been fully characterized in the available literature. The compound has a molecular weight of 377.49 g/mol, suggesting potential for drug-like properties. Standard PK studies including half-life, bioavailability, and tissue distribution would be required for in vivo studies. The compound is typically stored at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
Toxicological data for GR-46611 have not been reported in the available literature. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies would be required before any clinical development.
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| References |
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| Additional Infomation |
3-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N-[(4-methoxyphenyl)methyl]-2-acrylamide is a member of the tryptamine class of compounds.
GR-46611 is a 5-HT1D receptor agonist. It can be used in research on bladder hyperactivity and leukemia. Blockade of GR-46611-induced hypothermia in guinea pigs provides a model for studying centrally acting 5-HT1D receptor ligands. The compound has potential applications in neurological disorders including Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. GR-46611 is a research tool and is not approved for clinical use. |
| Molecular Formula |
C23H27N3O2
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|---|---|
| Molecular Weight |
377.47938
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| Exact Mass |
377.21
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| CAS # |
185259-85-2
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| PubChem CID |
6160690
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| Appearance |
White to off-white solid powder
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| Density |
1.168g/cm3
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| Boiling Point |
645.9ºC at 760mmHg
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| Flash Point |
344.4ºC
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| Vapour Pressure |
1.43E-16mmHg at 25°C
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| Index of Refraction |
1.639
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| LogP |
4.001
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
28
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| Complexity |
514
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C)CCC1C2C(=CC=C(/C=C/C(NCC3C=CC(OC)=CC=3)=O)C=2)NC=1
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| InChi Key |
LBVZWEWTNUDWNS-YRNVUSSQSA-N
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| InChi Code |
InChI=1S/C23H27N3O2/c1-26(2)13-12-19-16-24-22-10-6-17(14-21(19)22)7-11-23(27)25-15-18-4-8-20(28-3)9-5-18/h4-11,14,16,24H,12-13,15H2,1-3H3,(H,25,27)/b11-7+
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| Chemical Name |
(E)-3-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N-[(4-methoxyphenyl)methyl]prop-2-enamide
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~264.91 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 | 2.6491 mL | 13.2457 mL | 26.4915 mL | |
| 5 mM | 0.5298 mL | 2.6491 mL | 5.2983 mL | |
| 10 mM | 0.2649 mL | 1.3246 mL | 2.6491 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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