GR-46611 is a 5-HT1D receptor agonist (activator). GR-46611 may be utilized in research on hyperactive bladder and leukemia.

Physicochemical Properties

Molecular Formula	C23H27N3O2
Molecular Weight	377.47938
Exact Mass	377.21
CAS #	185259-85-2
PubChem CID	6160690
Appearance	White to off-white solid powder
Density	1.168g/cm3
Boiling Point	645.9ºC at 760mmHg
Flash Point	344.4ºC
Vapour Pressure	1.43E-16mmHg at 25°C
Index of Refraction	1.639
LogP	4.001
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	8
Heavy Atom Count	28
Complexity	514
Defined Atom Stereocenter Count	0
SMILES	CN(C)CCC1C2C(=CC=C(/C=C/C(NCC3C=CC(OC)=CC=3)=O)C=2)NC=1
InChi Key	LBVZWEWTNUDWNS-YRNVUSSQSA-N
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+
Chemical Name	(E)-3-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N-[(4-methoxyphenyl)methyl]prop-2-enamide
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: 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)

Biological Activity

ln Vitro	CEM cell proliferation is induced by GR-46611 (1 μM, 48 hours) [2].
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].
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%.
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%.
References	[1]. A 5-HT 1D -receptor agonist protects Dravet syndrome mice from seizure and early death. Eur J Neurosci. 2020 Nov;52(10):4370-4374. [2]. The proliferation of human T lymphoblastic cells induced by 5-HT1B receptors activation is regulated by 5-HT-moduline. C R Acad Sci III. 2001 Apr;324(4):365-72. [3]. Inhibition of bladder activity by 5-hydroxytryptamine1 serotonin receptor agonists in cats with chronic spinal cord injury. J Pharmacol Exp Ther. 2004 Sep;310(3):1266-72. [4]. Stimulation of central 5-HT1D receptors causes hypothermia in the guinea-pig. J Psychopharmacol. 1994 Jan;8(1):14-21.
Additional Infomation	3-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N-[(4-methoxyphenyl)methyl]-2-propenamide is a member of tryptamines.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~264.91 mM)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.