CL 316,243 (disodium salt)
目录号 : GC43276CL 316,243 (disodium salt) 是一种高效的 β3 肾上腺素受体选择性激动剂，EC50 为 3 nM。它是一种有效的脂肪细胞脂解刺激剂，可增加棕色脂肪组织的产热和代谢率，具有治疗肥胖症、糖尿病和急迫性尿失禁的潜力。
Cas No.:151126-84-0,138908-40-4
Sample solution is provided at 25 µL, 10mM.
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Related Biological Data
NIR-II fluorescence imaging and quantitative analysis of the ROI in normal mice and CL-treated mice. CL-treated mice were injected 20 μg CL316,243 (CL) intraperitoneally for 7 days.(b,c) ROI analysis of the iBAT-to-background and iBAT-to-liver ratios of normal mice and CL-treated mice
CL316,243(CL)-treated mice were kept at 22 °C and injected 20 μg CL316,243 (GLPBIO) intraperitoneally for 7 days.
ACS Applied Materials & Interfaces (2023). PMID: 37289581 IF: 10.3831 -
Related Biological Data
Geniposide negatively regulates UCP1 via suppressing transcription activity of UCP1. (A) Representative images of GFP intensity in HEK293T cells treated with DMSO, CL316243, or geniposide.(B) Relative level of GFP intensity in HEK293T cells treated with DMSO, CL316243, or geniposide (10 and 20 mg/ml) .
Relative level of GFP intensity in HEK293T cells treated with DMSO, CL316243(GlpBio), or geniposide (10 and 20 mg/ml) .
Toxicology (2021): 153014. PMID: 34718029 IF: 4.221 -
Related Biological Data
Letmd1 is critical for thermogenesis in BAT. (B-C) Relative mRNA expression of Ucp1 and Letmd1 in BAT following cold exposure or CL316,243 for 7 d or 10 d, b-actin was used as the internal control. WT mice following CL316,243 were kept at 22 ℃.
For NE and CL316,243(GlpBio) treatment,differentiated brown adipocytes were treated with 10 mM CL316,243 or 1 mM NE for 6 h.
Biochimie 201 (2022): 100-115. PMID: 35817133 IF: 3.9003
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| Cell experiment [1]: | |
Cell lines | White and brown preadipocytes |
Preparation Method | At the third day of culture CL 316,243 (disodium salt)（10 nM） or isoproterenol （1mM） was added to the culture medium . Cells were harvested at day 10 and analysed. |
Reaction Conditions | CL 316,243 (disodium salt) ( 10 nM ); 7 days |
Applications | In both types of adipocyte culture lipid accumulation was first detectable at day 6 (around confluence) . Until day 10 an almost linear increase in lipid content occurred. overall lipid accumulation was about 30% higher in white adipocyte cultures than in brown ones. |
| Animal experiment [2]: | |
Animal models | Insulin resistance model |
Preparation Method | Nine to ten week old male WT and MKR mice were injected intraperitoneally with CL-316,243 (1 mg/kg /day) or with an equivalent volume of vehicle (sterile water and phosphate buffered saline) for three weeks. |
| CL 316,243 (disodium salt) ( 1 mg/kg ; ip ), 3 weeks | |
Applications | After treatment with CL-316,243, the circulating glucose and insulin concentrations in the MKR mice improved, an increase in the expression of peroxisomal fatty acid oxidation genes was observed in addition to a decrease in the expression of retinaldehyde dehydrogenases. |
References: [1]. Klaus S, Seivert A, Boeuf S. Effect of the beta(3)-adrenergic agonist Cl316,243 on functional differentiation of white and brown adipocytes in primary cell culture. Biochim Biophys Acta. 2001 May 28;1539(1-2):85-92. | |
CL 316,243 (disodium salt)is a highly potent β3-adrenoceptor selective agonist with an EC50 of 3 nM. It is a potent adipocyte lipolysis stimulator that increases thermogenesis and metabolic rate of brown adipose tissue and has the potential to treat obesity, diabetes, and urge urinary incontinence[1].
CL 316,243 (disodium salt)(10 nM, 10 days) treated with white and brown adipocytes, lipid accumulation was first detected on day 6 (confluence) and lipid content increased almost linearly until day 10. Overall lipid accumulation in white adipocyte cultures was approximately 30% higher than in brown adipocyte cultures[2].CL 316,243 (disodium salt) inhibits spontaneously contracting, isolated rat detrusor strips in a concentration dependent manner with a mean concentration inhibiting 50% of maximal response of 2.65 nM[3].
Following treatment with CL 316,243 (disodium salt) (1 mg/kg; i.p.; 3 weeks), expression of peroxisomal FA oxidases ACAA1 and HSD17b4 was increased in adipose tissue of MKR mice[4].CL 316,243 (disodium salt) (1 mg/kg; SC; 2 weeks) reduced serum levels of glucose, insulin, triglycerides, free fatty acids, and tumor necrosis factor-α (TNF-α), and increased adiponectin[5]. CL 316,243 (disodium salt) (0.3 and 1 mg/kg; 2 weeks; subcutaneous injection) dose-dependently reduced the weight/volume of the inguinal fat pad [6].
[1].Bloom JD, Dutia MD, Johnson BD, Wissner A, Burns MG, Largis EE, Dolan JA, Claus TH. Disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino] propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316,243). A potent beta-adrenergic agonist virtually specific for beta 3 receptors. A promising antidiabetic and antiobesity agent. J Med Chem. 1992 Aug 7;35(16):3081-4.
[2]. Klaus S, Seivert A, Boeuf S. Effect of the beta(3)-adrenergic agonist Cl316,243 on functional differentiation of white and brown adipocytes in primary cell culture. Biochim Biophys Acta. 2001 May 28;1539(1-2):85-92.
[3]Woods M, Carson N, Norton NW, Sheldon JH, Argentieri TM. Efficacy of the beta3-adrenergic receptor agonist CL-316243 on experimental bladder hyperreflexia and detrusor instability in the rat. J Urol. 2001 Sep;166(3):1142-7.
[4]. Kumar A, Shiloach J, Betenbaugh MJ, Gallagher EJ. The beta-3 adrenergic agonist (CL-316,243) restores the expression of down-regulated fatty acid oxidation genes in type 2 diabetic mice. Nutr Metab (Lond). 2015 Mar 8;12:8.
[5]. Shin W, Okamatsu-Ogura Y, Matsuoka S, Tsubota A, Kimura K. Impaired adrenergic agonist-dependent beige adipocyte induction in obese mice. J Vet Med Sci. 2019 Jun 6;81(6):799-807.
[6]Danysz W, Han Y, Li F, Nicoll J, Buch P, Hengl T, Ruitenberg M, Parsons C. Browning of white adipose tissue induced by the ß3 agonist CL-316,243 after local and systemic treatment - PK-PD relationship. Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt B):2972-2982.
CL 316,243 (disodium salt) 是一种高效的 β3 肾上腺素受体选择性激动剂，EC50 为 3 nM。它是一种有效的脂肪细胞脂解刺激剂，可增加棕色脂肪组织的产热和代谢率，具有治疗肥胖症、糖尿病和急迫性尿失禁的潜力[1]。
CL 316,243 (disodium salt) ( 10 nM, 10 days )处理白色和棕色脂肪细胞，在第 6 天（汇合）首次检测到脂质积累。直到第 10 天，脂质含量几乎呈线性增加。白色脂肪细胞培养物中的总体脂质积累比棕色脂肪细胞培养物中高出约 30%[2]。CL 316243 以浓度依赖性方式抑制自发收缩的孤立大鼠逼尿肌条带，平均浓度抑制 2.65 nM 最大反应的 50% [3]。
CL 316,243 (disodium salt) (1mg/kg；ip；3周)治疗后，MKR小鼠脂肪组织中过氧化物酶体脂肪酸氧化酶ACAA1和HSD17b4的表达增加[4]。CL 316,243 (disodium salt)（1mg/kg；SC；2周）降低血清葡萄糖、胰岛素、甘油三酯、游离脂肪酸和肿瘤坏死因子-α（TNF-α）的水平，并升高脂联素[5]。CL 316,243 (disodium salt) ( 0.3 and 1mg/kg ；2周；SC) 剂量依赖性减少腹股沟脂肪垫重量/体积[6]。
| Cas No. | 151126-84-0,138908-40-4 | SDF | |
| 化学名 | 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylic acid, disodium salt | ||
| Canonical SMILES | ClC1=CC=CC([C@@H](O)CN[C@H](C)CC2=CC=C(OC(C([O-])=O)(C([O-])=O)O3)C3=C2)=C1.[Na+].[Na+] | ||
| 分子式 | C20H18ClNO7•2Na | 分子量 | 465.8 |
| 溶解度 | 0.5mg/ml in DMSO, PBS (pH 7.2): 3 mg/ml | 储存条件 | Desiccate at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1468 mL | 10.7342 mL | 21.4684 mL |
| 5 mM | 0.4294 mL | 2.1468 mL | 4.2937 mL |
| 10 mM | 0.2147 mL | 1.0734 mL | 2.1468 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
18F-FDG PET/CT monitoring of β3 agonist-stimulated brown adipocyte recruitment in white adipose tissue
J Nucl Med 2015 Jan;56(1):153-8.PMID:25525187DOI:10.2967/jnumed.114.147603.
There is rising interest in recruitment of brown adipocytes into white adipose tissue (WAT) as a means to augment energy expenditure for weight reduction. We thus investigated the potential of (18)F-FDG uptake as an imaging biomarker that can monitor the process of WAT browning. Methods: C57BL/6 mice were treated daily with the β3 agonist CL316,243 (5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylic acid disodium salt), whereas controls received saline. (18)F-FDG small-animal PET/CT was serially performed at 1 h after CL316,243 injection. After sacrifice, interscapular brown adipose tissue (BAT) and WAT depots were extracted, weighed, and measured for (18)F-FDG uptake. Tissues underwent immunostaining, and UCP1 content was quantified by Western blotting. Results: PET/CT showed low (18)F-FDG uptake in both BAT and inguinal WAT at baseline. BAT uptake was substantially increased by a single stimulation with CL316,243. Uptake in inguinal WAT was only modestly elevated by the first stimulation uptake but gradually increased to BAT level by prolonged stimulation. Ex vivo measurements recapitulated the PET findings, and measured (18)F-FDG uptake in other WAT depots was similar to inguinal WAT. WAT browning by prolonged stimulation was confirmed by a substantial increase in uncoupling protein 1 (UCP1), cytochrome-c oxidase 4 (COX4), and PR domain containing 16 (PRDM16) staining as markers of brown adipocytes. UCP1 content, which served as a measure for extent of browning, was low in baseline inguinal WAT but linearly increased over 10 d of CL316,243 injection. Finally, image-based and ex vivo-measured (18)F-FDG uptake in inguinal WAT correlated well with UCP1 content. Conclusion: (18)F-FDG PET/CT has the capacity to monitor brown adipocyte recruitment into WAT depots in vivo and may thus be useful for screening the efficacy of strategies to promote WAT browning.