| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
β3-adrenergic receptor
β3-adrenergic receptor (β3-AR). BRL37344 sodium salt is a selective β3 adrenoceptor agonist. Ki values are 287 nM for β3, 1750 nM for β1, and 1120 nM for β2 receptors. |
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| ln Vitro |
BRL37344, a β3-AR agonist, significantly decreased the amplitude, muscle force, and duration of the DSM contractions induced by 20 Hz EFS, in a concentration-dependent manner. This BRL37344-mediated inhibition of the amplitude and muscle force of the nerve-evoked DSM contraction was significantly reduced by iberiotoxin, a highly selective inhibitor of the BK channel, revealing a role for BK channels in the β3-AR-induced inhibition of human DSM nerve-evoked contractions. We further used atropine, α,β-methylene-ATP, and suramin to separate the cholinergic and purinergic components of human DSM nerve-evoked contractions. We found that the β3-AR agonist, BRL37344, inhibited both components of the EFS-induced (0.5–50 Hz) DSM contractions. [2]
In vitro, BRL37344 shows potent and selective activation of β3-adrenoceptors with Ki values of 287, 1750, and 1120 nM for β3, β1, and β2 receptors, respectively. The compound stimulates cAMP accumulation in cells expressing β3-AR, leading to downstream activation of protein kinase A and lipolytic pathways. |
| ln Vivo |
In obese mice, administration with BRL37344 sodium (BRL 37344A) dramatically lowers body weight [1]. Compared with the controls, the obese mice and DM mice showed successively lower 18F-FDG uptake in the interscapular BAT (P = 0.036 and < 0.001, respectively). After two-week BRL37344 treatment, the BAT uptake was significantly elevated in both obese mice (P = 0.010) and DM mice (P = 0.004), accompanied with significantly decreased blood glucose levels (P = 0.023 and 0.036, respectively). The BAT uptake was negatively correlated with the blood glucose levels in both obese mice (r = -0.71, P = 0.003) and DM mice (r = -0.74, P = 0.010). BRL37344 treatment also caused significant weight loss in the obese mice (P = 0.001). Levothyroxine treatment increased the BAT uptake in the control mice (P = 0.025) and obese mice (P = 0.013), but not in the DM mice (P = 0.45).
Conclusion: The inhibited BAT function in obese and DM mice can be re-activated by β3-adrenergic receptor agonist or thyroid hormone, and effective BAT activation may lead to weight loss and blood glucose lowering. Activating BAT can provide a new treatment strategy for obesity and DM. [1]
In vivo, BRL37344 is used to study β3-AR-mediated physiological effects including lipolysis, thermogenesis, and cardiac function modulation. It has been employed in animal models to investigate the role of β3-adrenoceptors in metabolic regulation and energy homeostasis. Detailed in vivo efficacy data are available in published literature. |
| Enzyme Assay |
Non-cell receptor binding assays are performed using membrane preparations from cells expressing human or rodent β1, β2, and β3 adrenoceptors. Radioligand binding studies are conducted using [¹²⁵I]iodocyanopindolol as a tracer. Membranes are incubated with the radioligand and varying concentrations of BRL37344 (0.01-100 μM). Nonspecific binding is determined with propranolol. After incubation at 37°C for 60 minutes, filtration and scintillation counting are performed. Ki values are calculated from competition curves.
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| Cell Assay |
Isometric DSM tension recordings [2]
Isometric DSM tension recordings were conducted as previously described. Briefly, mucosa-free DSM tissues from humans were dissected into strips 5–7 mm long and 2–3 mm wide. DSM strips were clipped between a stationary mount and a force-displacement transducer then placed in tissue baths filled with Ca2+-containing physiological saline solution (PSS) (§Solutions and Drugs) thermostatically controlled at 37°C and aerated with 95% O2 and 5% CO2. Tissue baths were equipped with platinum electrodes for EFS. EFS pulses had 20 V amplitude, 0.75 ms width, 3 s stimulus duration, and polarity was reversed for alternating pulses. Then, DSM strips were stretched to 10 mN of initial tension and the bath solution was changed with fresh PSS every 15 min during an equilibration period of 45 to 60 min. Following the equilibration period, two different EFS protocols were generated using PHM-152I stimulator and the DSM response to EFS was recorded using MyoMed software. Compounds were applied only to DSM strips with stable pre-compound controls following the equilibration period. In the first EFS protocol, a 20 Hz EFS frequency was applied continuously every minute to generate DSM nerve-evoked contractions. In the second EFS protocol, nerve-evoked DSM contractions were generated by applying increasing EFS frequencies (0.5, 2, 3.5, 5, 7.5, 10, 12.5, 15, 20, 30, 40, 50 Hz) every 3 min. Researchers evaluated the BRL 37344 inhibitory effects on DSM contractions induced by EFS in the absence or presence of iberiotoxin, a selective BK channel blocker; atropine, a cholinergic blocker; suramin, a purinergic receptor blocker; and α,β-methylene-ATP, a purinergic receptor agonist. Cellular assays are performed using cell lines (e.g., CHO or HEK-293) transfected with β3-adrenoceptors. Cells are treated with BRL37344 at concentrations ranging from 0.1 nM to 100 μM. Functional activity is measured by quantifying intracellular cAMP accumulation using competitive ELISA or HTRF assays. The EC₅₀ for cAMP stimulation is determined from dose-response curves. β3 selectivity is confirmed by parallel assays using β1- and β2-expressing cells. |
| Animal Protocol |
Animal/Disease Models: Fiveweeks old male imprinted control region (ICR) mice [1]
Doses: 2.5 mg/kg Route of Administration: intraperitoneal (ip) injection; three times a week for two weeks Experimental Results: diminished the body weight of obese mice. Obese mice were established by a high-fat diet for eight weeks, and diabetes mellitus(DM) models were induced with Streptozocin in obese mice. 18F-FDG microPET was used to monitor BAT function during obese and DM modeling, and also after BRL37344 (a β3-adrenergic receptor agonist) or levothyroxine treatment. The BAT function was correlated with the body weight and blood glucose levels. [1] In vivo studies are conducted in rodent models. BRL37344 is administered via intraperitoneal or intravenous routes at doses typically ranging from 0.01-10 mg/kg. Thermoregulation and metabolic rate are measured using indirect calorimetry. Lipolysis is assessed by measuring plasma free fatty acid and glycerol levels. Cardiac function is evaluated by electrocardiography or echocardiography. Tissue distribution and receptor occupancy may also be assessed. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of BRL37344 have been studied in preclinical species. Following intravenous administration, the compound shows rapid distribution and elimination. The half-life is relatively short, consistent with its use as a pharmacological tool rather than a therapeutic agent. Oral bioavailability is limited. The compound is metabolized by hepatic enzymes and excreted primarily in urine.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for BRL37344 are limited to research use. At high doses, β3-agonism may cause cardiovascular effects including tachycardia and increased cardiac contractility. No significant organ-specific toxicity has been reported at pharmacological doses. Standard safety pharmacology studies would be required for therapeutic development.
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| References | |
| Additional Infomation |
β-Adrenergic agonists: Drugs that selectively bind to and activate β-adrenergic receptors. This study revealed that the β3-adrenergic agonist BRL37344 effectively reduced nerve-induced contractions of the human detrusor muscle. We discovered for the first time that the relaxation effect of nerve-induced contractions of the human detrusor muscle mediated by β3-adrenergic agonists depends on the BK channel, highlighting the key role of the BK channel in the physiological function of the human detrusor muscle. Future studies using detrusor muscle tissue from patients with overactive bladder (OAB) and detrusor overactivity are expected to confirm a similar functional relationship between β3-adrenergic agonists and the BK channel, which will further promote the research of potential pharmacological targets in this field for the treatment of overactive bladder. [2]
BRL37344 sodium salt is a research compound developed by GlaxoSmithKline. It is widely used as a pharmacological tool to study β3-adrenoceptor function in metabolism, obesity, and cardiovascular research. The compound's selectivity profile (Ki: β3 287 nM, β1 1750 nM, β2 1120 nM) makes it useful for distinguishing β3-mediated effects from those mediated by β1 and β2 receptors. It is not approved for clinical use. |
| Molecular Formula |
C19H21CLNNAO4
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|---|---|
| Molecular Weight |
385.8198
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| Exact Mass |
385.106
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| Elemental Analysis |
C, 59.15; H, 5.49; Cl, 9.19; N, 3.63; Na, 5.96; O, 16.59
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| CAS # |
127299-93-8
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| Related CAS # |
90730-96-4 (free acid); 114333-71-0 (free acid); 127299-93-8 (sodium)
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| PubChem CID |
2436
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| Appearance |
White to off-white solid powder
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| Boiling Point |
569.7ºC at 760mmHg
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| Flash Point |
298.4ºC
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| Vapour Pressure |
8.09E-14mmHg at 25°C
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| LogP |
2.113
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
9
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| Heavy Atom Count |
26
|
| Complexity |
407
|
| Defined Atom Stereocenter Count |
0
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| InChi Key |
SNJIJYKMYQRHRC-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C19H22ClNO4.Na/c1-13(21-11-18(22)15-3-2-4-16(20)10-15)9-14-5-7-17(8-6-14)25-12-19(23)24;/h2-8,10,13,18,21-22H,9,11-12H2,1H3,(H,23,24);/q;+1/p-1
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| Chemical Name |
sodium;2-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetate
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| Synonyms |
BRL 37344; BRL-37344; BRL-37344 sodium; 127299-93-8; BRL 37344 sodium; BRL 37344, SODIUM SALT; Brl 37344A; brl37344 sodium salt; UNII-H7P384313Z; H7P384313Z; BRL37344
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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, avoid exposure to moisture. |
| 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 : ~5 mg/mL (~12.96 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 10 mg/mL (25.92 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5919 mL | 12.9594 mL | 25.9188 mL | |
| 5 mM | 0.5184 mL | 2.5919 mL | 5.1838 mL | |
| 10 mM | 0.2592 mL | 1.2959 mL | 2.5919 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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