| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
β3 adrenoceptor
CL 316243 free acid targets the beta-3 adrenergic receptor (beta3-AR), which is predominantly expressed in brown and white adipose tissue, as well as the bladder. It is a potent agonist with an EC50 of 3 nM. In contrast, it has extremely poor activity (low efficacy) at beta1/2-AR subtypes. Upon binding, it activates adenylate cyclase via the stimulatory G-protein (Gs), increasing intracellular cAMP levels. This leads to stimulation of lipolysis, increases thermogenesis, and enhances glucose uptake. |
|---|---|
| ln Vitro |
The IC50 values of CL 316243 free acid for rat heart and rat soleus muscle are 0.6 μM and 1 μM, respectively[1]. CL 316243 free acid inhibits spontaneous contraction of isolated rat detrusor muscle strips in a concentration-dependent manner, with the mean concentration inhibiting 50% of the maximal response being 2.65 nM[3].
In vitro, CL 316243 is a potent and selective beta3-AR agonist. Its activity is measured in cells overexpressing the beta3 receptor. Cells are treated with varying concentrations of CL 316243 (0.1 nM - 1 uM), and the downstream production of cAMP is measured using a HTRF (Homogeneous Time-Resolved Fluorescence) assay kit. The EC50 is confirmed to be approximately 3 nM. It is an effective stimulant of adipocyte lipolysis, which can be measured by free fatty acid release in isolated adipocytes. |
| ln Vivo |
CL316243 free acid (subcutaneous injection; 0.1 mg/kg/d; once daily; 1 week) increases the mRNA and protein expression levels of UCP1 in BAT, independent of diet [2].
In vivo, CL 316243 is used to activate brown adipose tissue (BAT) and induce white adipose tissue (WAT) browning. Administration to rodents results in a dose-dependent increase in oxygen consumption and body temperature (thermogenesis). It also stimulates lipolysis, leading to a reduction in fat mass and improvement in insulin sensitivity. These effects make it a promising candidate for the research and development of treatments for obesity and type 2 diabetes. |
| Enzyme Assay |
A non-cellular assay is not applicable, as it is a receptor agonist. A standard binding assay is used to measure its affinity. Membranes from CHO cells expressing the human beta3-AR are incubated with a radioligand like [¹2⁵I]Iodocyanopindolol (CYP) in the presence of varying concentrations (0.01 nM - 10 uM) of CL 316243. The reaction is filtered, and the radioactivity is counted. The Ki (inhibition constant) is calculated, which should be in the low nanomolar range, confirming its high affinity.
|
| Cell Assay |
CHO-K1 cells stably expressing the human beta3-adrenergic receptor are seeded in 96-well plates. The cells are treated with varying concentrations of CL 316243 (0.001-1000 nM) for 30 minutes. The cells are lysed, and intracellular cAMP levels are measured using a luminescence-based cAMP detection kit. The EC50 is calculated as the concentration required to produce 50% of the maximal cAMP response. The EC50 for CL 316243 is 3 nM.
|
| Animal Protocol |
Animal/Disease Models: Male C57BL/6J mice fed with high-fat diets (HFD; 45%-kcal fat) or a control diet (ND; 10%-kcal fat) for 14 weeks[2]
Doses: 0.1 mg/kg/day Route of Administration: S.c.; once a day; 1 weeks Experimental Results: Exhibited a premium effect of obesity in mice. To study the effect on energy metabolism, a mouse model of diet-induced obesity (DIO) is used. C57BL/6J mice are fed a high-fat diet for 10-16 weeks. CL 316243 is administered via intraperitoneal (IP) injection at doses of 0.1, 0.5, and 1.0 mg/kg, daily for 4 weeks. Body weight and food intake are monitored. After treatment, the animals are placed in metabolic chambers to measure oxygen consumption (VO2) and heat production. Brown and white adipose tissue depots are harvested to measure markers of thermogenesis (e.g., UCP-1 expression). |
| ADME/Pharmacokinetics |
CL 316243 has a molecular weight of 401.84 and a predicted LogP of 2.55, indicating moderate lipophilicity. Following intraperitoneal or subcutaneous injection in mice, it is rapidly absorbed. It has a moderate clearance rate and a short half-life (approximately 1-2 hours). As a potent beta3-agonist, it must be handled carefully to avoid triggering unwanted physiological effects. For research use, it is stored as a powder at -20degC, where it is stable for 2-3 years.
|
| Toxicity/Toxicokinetics |
As a potent beta-AR agonist, CL 316243 is a research chemical and not a drug. It may cause a decrease in blood pressure, increased heart rate (due to beta1-AR activity at high doses), and hypothermia at high doses. Standard safety precautions (gloves, lab coat, goggles) should be used. It is a moderate eye and skin irritant. It is for research use only and is not for human consumption.
|
| References |
|
| Additional Infomation |
CL 316243 is the free acid form of the potent beta3-AR agonist, CL 316,243. It is a standard "tool compound" in metabolic research, critically used to validate the role of beta3-AR in activating brown fat and treating obesity. Its high selectivity over beta1/2-AR allows researchers to dissect specific beta3-AR mediated pathways without the confounding effects of cardiac or bronchial stimulation. It is for research use only.
|
| Molecular Formula |
C20H20CLNO7
|
|---|---|
| Molecular Weight |
421.83
|
| Exact Mass |
421.093
|
| CAS # |
183720-02-7
|
| Related CAS # |
CL 316243; 138908-40-4
|
| PubChem CID |
5486546
|
| Appearance |
White to off-white solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Boiling Point |
689.5±55.0 °C at 760 mmHg
|
| Flash Point |
370.8±31.5 °C
|
| Vapour Pressure |
0.0±2.3 mmHg at 25°C
|
| Index of Refraction |
1.635
|
| LogP |
3.11
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
29
|
| Complexity |
589
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
ClC1=CC=CC(=C1)[C@H](CN[C@H](C)CC1=CC=C2C(=C1)OC(C(=O)O)(C(=O)O)O2)O
|
| InChi Key |
JEDJMKTVUPSHFW-ABAIWWIYSA-N
|
| InChi Code |
InChI=1S/C20H20ClNO7/c1-11(22-10-15(23)13-3-2-4-14(21)9-13)7-12-5-6-16-17(8-12)29-20(28-16,18(24)25)19(26)27/h2-6,8-9,11,15,22-23H,7,10H2,1H3,(H,24,25)(H,26,27)/t11-,15+/m1/s1
|
| Chemical Name |
5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylic acid
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~237.06 mM; with ultrasonication)
|
|---|---|
| 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 | 2.3706 mL | 11.8531 mL | 23.7062 mL | |
| 5 mM | 0.4741 mL | 2.3706 mL | 4.7412 mL | |
| 10 mM | 0.2371 mL | 1.1853 mL | 2.3706 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
