| Size | Price | Stock | Qty |
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| Targets |
β3-adrenergic receptor[1]
BRL-37344 targets the beta3-adrenergic receptor (beta3-AR), a G-protein coupled receptor (GPCR) primarily expressed in adipose tissue (both white and brown fat), the gallbladder, and the urinary bladder. Activation of beta3-AR stimulates lipolysis in white adipose tissue (WAT) and thermogenesis in brown adipose tissue (BAT) through the activation of adenylate cyclase and the production of cAMP. beta3-AR is a therapeutic target for obesity, overactive bladder, and metabolic disorders. |
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| ln Vitro |
In vitro, BRL-37344 is a potent and selective beta3-adrenergic receptor (beta3-AR) agonist. Its binding affinity for beta3-AR is Ki = 287 nM, with weaker affinity for beta1-AR (Ki = 1750 nM) and beta2-AR (Ki = 1120 nM), demonstrating selectivity for the beta3-AR subtype. The compound activates beta3-AR, leading to increased intracellular cAMP production. This activation results in lipolysis and thermogenesis in adipocytes. No specific EC50 values for cAMP accumulation or other functional assays are reported in the search results.
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| ln Vivo |
In vivo, BRL-37343 (the sodium salt) has been shown to dramatically lower body weight in obese mice upon administration. The compound is a specific beta3-adrenergic receptor agonist, and its weight-reducing effects are attributed to increased thermogenesis in brown adipose tissue (BAT) and lipolysis in white adipose tissue (WAT). No specific dosing information, animal models (e.g., diet-induced obese mice, ob/ob mice), or detailed efficacy data (percentage weight loss, metabolic rate changes) are provided in the search results.
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| Enzyme Assay |
The binding affinity of BRL-37344 to beta1, beta2, and beta3 adrenergic receptors is measured by competition binding assays using membrane preparations from cells expressing the recombinant human receptors. Radioligands such as [¹2⁵I]-iodocyanopindolol (ICYP) or [3H]-CGP-12177 are used. The compound is incubated with membranes and the radioligand for 60-90 minutes at room temperature. Nonspecific binding is determined using 1 microM propranolol. The radioactivity is measured by filtration and scintillation counting. Ki values (287 nM for beta3, 1750 nM for beta1, 1120 nM for beta2) are calculated from IC50 using the Cheng-Prusoff equation. Functional potency (EC50) for cAMP accumulation is measured in cells expressing the receptors.
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| Cell Assay |
For cellular cAMP assays, CHO-K1 or HEK293 cells stably expressing human beta3-AR are seeded in 96-well plates. Cells are treated with BRL-37344 at graded concentrations (0.1 nM-100 microM) for 15-30 minutes at 37degC. The reaction is terminated by cell lysis, and intracellular cAMP levels are measured using a competitive ELISA or HTRF (Homogeneous Time-Resolved Fluorescence) cAMP kit. The EC50 for cAMP accumulation is calculated. For adipocyte functional assays, primary white adipocytes or brown adipocytes are isolated from mouse adipose tissue or differentiated from preadipocyte cell lines (e.g., 3T3-L1). Cells are treated with BRL-37344, and glycerol release (a measure of lipolysis) is measured by a colorimetric or fluorometric assay. No specific EC50 values are reported.
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| Animal Protocol |
For in vivo evaluation of anti-obesity effects, male C57BL/6 mice are fed a high-fat diet (HFD) for 12-16 weeks to induce obesity. The mice are then administered BRL-37344 (or its sodium salt, BRL-37344A) intraperitoneally (IP) or orally at doses of 1-10 mg/kg daily for 2-4 weeks. Body weight and food intake are measured daily or every 2-3 days. Body composition (fat mass vs. lean mass) is assessed by EchoMRI or DEXA scanning. At the study endpoint, metabolic rate is measured by indirect calorimetry (oxygen consumption, CO2 production, heat production). Adipose tissue depots (gonadal, subcutaneous, brown) are harvested and weighed. Thermogenesis markers (UCP1 expression) in BAT are measured by qPCR and Western blot. Serum levels of triglycerides, free fatty acids, and glucose are measured.
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| ADME/Pharmacokinetics |
BRL-37344 (C1₉H22ClNO4, MW = 363.84, CAS 90730-96-4) is a solid powder. For storage, the compound should be kept at -20degC sealed, away from moisture and light. For in vitro use, stock solutions in DMSO (10-50 mM) can be stored at -80degC for up to 6 months or at -20degC for 1 month. For in vivo use, it can be formulated in 10% DMSO / 40% PEG300 / 5% Tween-80 / 45% saline or 0.5% methylcellulose/0.1% Tween-80. The sodium salt (BRL-37344A) is more water-soluble. No detailed PK parameters (oral bioavailability, Cmax, Tmax, half-life) are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for BRL-37344 are reported in the search results. As a research-grade beta3-AR agonist, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed, including the use of gloves, lab coat, and safety goggles. beta3-AR agonists in general have been studied for obesity and overactive bladder. Mirabegron (beta3-AR agonist) is FDA-approved for overactive bladder, indicating that beta3-AR activation can be safe in humans at appropriate doses. However, BRL-37344 is a research tool and has not undergone formal toxicity studies.
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| References | |
| Additional Infomation |
See also: BRL 37344 (Note moved to).
BRL-37344 is a potent and selective beta3-adrenergic receptor (beta3-AR) agonist. beta3-AR is a GPCR expressed predominantly in brown and white adipose tissue, where it regulates lipolysis and thermogenesis. Activation of beta3-AR in brown adipose tissue (BAT) increases non-shivering thermogenesis, while its activation in white adipose tissue (WAT) increases lipolysis, releasing free fatty acids. BRL-37344 has been widely used as a research tool to study the role of beta3-AR in metabolism, obesity, and energy balance. The compound is for research use only and has not received regulatory approval for any indication. The compound is also referred to as Fosigotifator (THAM sodium) in some sources. BRL-37344 is distinct from the more commonly known beta3-AR agonist CL-316,243, but both are used for obesity research. |
| Molecular Formula |
C19H22CLNO4
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|---|---|
| Molecular Weight |
363.84
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| Exact Mass |
363.123
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| CAS # |
90730-96-4
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| PubChem CID |
2437
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| Appearance |
Solid powder
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| LogP |
0.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
25
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| Complexity |
401
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C[C@@H](CC1=CC=C(C=C1)OCC(=O)O)NC[C@H](C2=CC(=CC=C2)Cl)O
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| InChi Key |
ZGGNJJJYUVRADP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H22ClNO4/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)
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| Chemical Name |
2-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetic acid
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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 |
| 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 : 20 mg/mL (54.97 mM; ultrasonic and adjust pH to 3 with 1 M HCL)
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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 | 2.7485 mL | 13.7423 mL | 27.4846 mL | |
| 5 mM | 0.5497 mL | 2.7485 mL | 5.4969 mL | |
| 10 mM | 0.2748 mL | 1.3742 mL | 2.7485 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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