CL 316243

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.