| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
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| Targets |
β3-adrenergic receptor
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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]
|
| 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]
|
| 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. |
| 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] |
| References | |
| Additional Infomation |
Adrenergic beta-Agonists:
Drugs that selectively bind to and activate beta-adrenergic receptors.
The present study reveals that the β3-AR agonist, BRL37344, is very effective in reducing human DSM nerve-evoked contractions. We reveal for the first time that the β3-AR-agonist-mediated relaxation of human DSM nerve-evoked contractions is BK channel-dependent, emphasizing the critical role of BK channels in human DSM physiology. Future studies using DSM tissue from patients with OAB and detrusor overactivity are anticipated to demonstrate a similar functional relationship between β3-ARs and the BK channel, which would provide further impetus for studying potential pharmacologic targets in this area for the treatment of OAB.[2] |
| Molecular Formula |
C19H21CLNNAO4
|
|---|---|
| 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
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| Rotatable Bond Count |
9
|
| Heavy Atom Count |
26
|
| Complexity |
407
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| Defined Atom Stereocenter Count |
0
|
| InChi Key |
SNJIJYKMYQRHRC-UHFFFAOYSA-M
|
| 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
|
| Chemical Name |
sodium;2-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetate
|
| 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
|
| 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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