Solabegron
(Synonyms: 3'-[[2-[(2R)-2-(3-氯苯基)-2-羟基乙基]氨基]乙基]氨基]-[1,1'-联苯基]-3-羧酸,GW 427353) 目录号 : GC34808
Solabegron(GW427353)是β3肾上腺素能受体(β3-AR)的选择性激动剂,在中国仓鼠卵巢细胞中测得的EC50值为22nM。目前正在被用于开发治疗膀胱过度活跃和肠易激综合征。
Cas No.:252920-94-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Solabegron (GW 427353) is a selective β3-adrenergic receptor agonist, stimulating cAMP accumulation in Chinese hamster ovary cells expressing the human β3-AR, with an EC50 value of 22 nM[1]. Solabegron (GW 427353) is being developed for the treatment of overactive bladder and irritable bowel syndrome[1]. EC50: 22 nM (β3-AR in cells)[1].
Solabegron (GW427353) at 3 mg/kg i.v. evokes an increase in micturition volume threshold that prevented the acetic acid-evoked decreases in dogs. The low dose (1 mg/kg) shows no significant activity[1]. Animal Model: Adult female beagle dogs (6-10 kg)[1].
[1]. Hicks A, et al. GW427353 (solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog. J Pharmacol Exp Ther. 2007 Oct;323(1):202-9. [2]. Andersson KE, et al. Selective β3-adrenoceptor agonists for the treatment of overactive bladder. J Urol. 2013 Oct;190(4):1173-80.
| Cas No. | 252920-94-8 | SDF | |
| 别名 | 3'-[[2-[(2R)-2-(3-氯苯基)-2-羟基乙基]氨基]乙基]氨基]-[1,1'-联苯基]-3-羧酸,GW 427353 | ||
| Canonical SMILES | O=C(C1=CC(C2=CC=CC(NCCNC[C@@H](C3=CC=CC(Cl)=C3)O)=C2)=CC=C1)O | ||
| 分子式 | C23H23ClN2O3 | 分子量 | 410.89 |
| 溶解度 | DMSO: 250 mg/mL (608.44 mM) | 储存条件 | 4°C, protect from light |
| 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 | 2.4337 mL | 12.1687 mL | 24.3374 mL |
| 5 mM | 0.4867 mL | 2.4337 mL | 4.8675 mL |
| 10 mM | 0.2434 mL | 1.2169 mL | 2.4337 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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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。
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Solabegron: a potential future addition to the β-3 adrenoceptor agonist armamentarium for the management of overactive bladder
Expert Opin Investig Drugs 2015 Mar;24(3):413-9.PMID:25557359DOI:10.1517/13543784.2015.1001836.
Introduction: Overactive bladder (OAB) affects many women and men worldwide and has a significant adverse effect on a person's quality of life. Historically, behavioral therapy and anti-muscarinic agents have been the primary therapies used in the management of OAB. However, persistence with anti-muscarinic therapy has been limited. The role of β-3 agonists is established in the management of OAB with the first β-3 agonist recently approved by the FDA. Solabegron is one such selective β-3 agonist currently under investigation. Areas covered: In this review, the authors discuss animal studies, in vitro human bladder strip and Phase II studies, which suggest a role for Solabegron in the management of OAB. The authors also discuss its potential role in combination therapy. Expert opinion: Phase II studies with Solabegron support its potential future role in the management of OAB. However, further studies are needed to establish its efficacy and safety as well as to allow its clinical comparison with current therapies.
Cryo-EM structures of the β3 adrenergic receptor bound to Solabegron and isoproterenol
Biochem Biophys Res Commun 2022 Jun 30;611:158-164.PMID:35489202DOI:10.1016/j.bbrc.2022.04.065.
The β3-adrenergic receptor (β3AR) is the most essential drug target for overactive bladder and has therapeutic potentials for the treatments of type 2 diabetes and obesity. Here, we report the cryo-electron microscopy structures of the β3AR-Gs signaling complexes with the selective agonist, Solabegron and the nonselective agonist, isoproterenol. Comparison of the isoproterenol-, mirabegron-, and solabegron-bound β3AR structures revealed that the extracellular loop 2 changes its conformation depending on the bound agonist and plays an essential role in Solabegron binding. Moreover, β3AR has an intrinsically narrow exosite, regardless of the agonist type. This structural feature clearly explains why β3AR prefers mirabegron and Solabegron, as the narrow exosite is suitable for binding with agonists with elongated shapes. Our study deepens the understanding of the binding characteristics of β3AR agonists and may pave the way for developing β3AR-selective drugs.
Drugs Currently Undergoing Preclinical or Clinical Trials for the Treatment of Overactive Bladder: A Review
Curr Ther Res Clin Exp 2022 Apr 6;96:100669.PMID:35494662DOI:10.1016/j.curtheres.2022.100669.
Background: Overactive bladder (OAB) is a common clinical condition for which current drug treatment comprises drugs blocking the cholinergic nerve supply, or augmenting the adrenergic nerve supply, to the detrusor muscle of the urinary bladder. Current treatments have drawbacks, including lack of efficacy and the development of adverse effects in some patients. Hence, new and better drugs for treating OAB will be clinically useful. Objective: This review is meant to provide information on drugs currently undergoing preclinical or clinical trials for the treatment of OAB published in journal articles or elsewhere. Methods: The cited articles were retrieved from PubMed and Google Scholar from January 1, 1990, to December 31, 2021. The search terms used were contraction or contractility, detrusor, inhibition, isolated or in vitro, in vivo, overactive bladder, and relaxant effect or relaxation. Results: There are 4 classes of new drugs under various stages of development for the treatment of OAB. These are drugs acting on the autonomic nerve supply to the detrusor muscle of the urinary bladder that include the anticholinergics tarafenacin and afacifenacin and the β3 adrenoceptor agonists Solabegron and ritobegron; drugs acting on ion channels in the detrusor muscle (eg, potassium channel openers and calcium channel blockers), drugs acting on cellular enzymes like phosphodiesterase-5 inhibitors and Rho kinase inhibitors, and drugs acting on miscellaneous targets (eg, pregabalin and trimetazidine). Conclusions: Drugs currently used to treat OAB target only the cholinergic and adrenergic cellular signalling pathways. There are many other drugs under trial targeting other cellular pathways that may be useful for treating OAB. Their approval for clinical use might improve the treatment of patients with OAB. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX).
GW427353 (Solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog
J Pharmacol Exp Ther 2007 Oct;323(1):202-9.PMID:17626794DOI:10.1124/jpet.107.125757.
Functional studies have demonstrated that adrenoceptor agonist-evoked relaxation is mediated primarily by beta3-adrenergic receptors (ARs) in human bladder. Thus, the use of selective beta3-AR agonists in the pharmacological treatment of overactive bladder is being explored. The present studies investigated the effects of a novel selective beta3-AR agonist, (R)-3'-[[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-[1,1'-biphenyl]-3-carboxylic acid (GW427353; Solabegron) on bladder function in the dog using in vitro and in vivo techniques. GW427353 stimulated cAMP accumulation in Chinese hamster ovary cells expressing the human beta3-AR, with an EC50 value of 22 +/- 6 nM and an intrinsic activity 90% of isoproterenol. At concentrations of 10,000 nM, GW427353 produced a minimal response in cells expressing either beta1-ARs or beta2-ARs (maximum response <10% of that to isoproterenol). In dog isolated bladder strips, GW427353 evoked relaxation that was attenuated by the nonselective beta-AR antagonist bupranolol and 1-(2-ethylphenoxy)-3-[[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]-(2S)-2-propanol (SR59230A) (reported to have beta3-AR antagonist activity). The relaxation was unaffected by atenolol, a selective beta1-AR antagonist, or (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI 118551), a selective beta2-AR antagonist. GW427353 increased the volume required to evoke micturition in the anesthetized dog following acetic acid-evoked bladder irritation, without affecting the ability of the bladder to void. GW427353-evoked effects on bladder parameters in vivo were inhibited by bupranolol. The present study demonstrates that selective activation of beta3-AR with GW427353 evokes bladder relaxation and facilitates bladder storage mechanisms in the dog.
A multicenter, double-blind, randomized, placebo-controlled trial of the β3-adrenoceptor agonist Solabegron for overactive bladder
Eur Urol 2012 Nov;62(5):834-40.PMID:22695239DOI:10.1016/j.eururo.2012.05.053.
Background: β-Adrenoceptor agonists are effective in animal models of bladder dysfunction, and the human bladder primarily expresses the β3 receptor subtype. Objective: To evaluate the efficacy and tolerability of the highly selective and potent β3-adrenoceptor agonist Solabegron in a clinical proof-of-concept study in incontinent women with overactive bladder (OAB). Design, setting, and participants: This was a randomized, double-blind trial in adult women with OAB (one or more 24-h incontinence episodes and eight or more average 24-h micturitions). Interventions: Solabegron 50 mg (n=88), Solabegron 125 mg (n=85), or placebo (n=85)-all twice daily-were administered. Outcome measurements and statistical analysis: The primary efficacy end point was percentage change from baseline to week 8 in the number of incontinence episodes over 24 h. Secondary end points included actual change and percentage change from baseline to week 4 and week 8 in micturitions per 24 h, urgency episodes per 24 h, and volume voided per micturition. Adverse events (AEs) were assessed, as well. Results and limitations: Solabegron 125 mg produced a statistically significant difference in percent change from baseline to week 8 in incontinence episodes over 24h when compared with placebo (p=0.025). Solabegron 125 mg treatment also showed statistically significant reductions from baseline to weeks 4 and 8 in micturitions over 24 h and a statistically significant increase from baseline to week 8 in urine volume voided. Solabegron was well tolerated, with a similar incidence of AEs in each treatment group. There were no significant treatment differences for mean changes from baseline to week 8 in systolic blood pressure (BP), diastolic BP, mean arterial pressure (MAP), or heart rate during the 24-h ambulatory measurement. Conclusions: Solabegron significantly reduced the symptoms of OAB in women with moderate to severe OAB. Solabegron was safe, well tolerated, and did not demonstrate significant differences in AEs as compared to placebo. β3-Adrenoceptor agonists may represent a new therapeutic approach for treating OAB symptoms.