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]。