Vibegron
(Synonyms: MK-4618) 目录号 : GC63254
Vibegron (MK-4618) 是一种有效的，高选择性的 β3-adrenoceptor 激动剂(EC50=1.1 nM)。Vibegron 可用于膀胱过度活动相关的严重急症尿失禁。
Cas No.:1190389-15-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Vibegron (MK-4618) is a potent, highly selective β3-adrenoceptor agonist (EC50=1.1 nM). Vibegron can be used for severe urgency urinary incontinence related to overactive bladder[1][2][3].
Vibegron (1~12 μμ; i.v.) exhibits dose dependent decreases in micturition pressure and increases in functional bladder capacity[3].Vibegron (30 mg/kg; p.o.; 4 weeks) upregulates mRNA levels of type 1, type 3 collagen, TGF‐β1, and HIF‐1α[4].Vibegron (1 and 10 mg/kg; i.v.; interval 30 minutes) (10 mg/kg) in oxo-M-treated rats makes bladder capacity significantly decreased compared with oxo-M-not treated rats (intravesical instillation of vehicle)[5].
[1]. Yoshida M, et al. Efficacy of vibegron, a novel β3-adrenoreceptor agonist, on severe urgency urinary incontinence related to overactive bladder: post hoc analysis of a randomized, placebo-controlled, double-blind, comparative phase 3 study. BJU Int. 2020;125(5):709-717.
[2]. Yoshida M, et al. Efficacy of novel β3 -adrenoreceptor agonist vibegron on nocturia in patients with overactive bladder: A post-hoc analysis of a randomized, double-blind, placebo-controlled phase 3 study. Int J Urol. 2019;26(3):369-375.
[3]. Edmondson SD, et al. Discovery of Vibegron: A Potent and Selective β3 Adrenergic Receptor Agonist for the Treatment of Overactive Bladder. J Med Chem. 2016;59(2):609-623.
[4]. Gotoh D, et al. Effects of a new β3-adrenoceptor agonist, vibegron, on neurogenic bladder dysfunction and remodeling in mice with spinal cord injury. Neurourol Urodyn. 2020;39(8):2120-2127.
[5]. Furuta A, et al. Additive effects of intravenous and intravesical application of vibegron, a β3-adrenoceptor agonist, on bladder function in rats with bladder overactivity. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(11):2073-2080.
| Cas No. | 1190389-15-1 | SDF | |
| 别名 | MK-4618 | ||
| 分子式 | C26H28N4O3 | 分子量 | 444.53 |
| 溶解度 | 储存条件 | 4°C, away from moisture and 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 | 2.2496 mL | 11.2478 mL | 22.4957 mL |
| 5 mM | 0.4499 mL | 2.2496 mL | 4.4991 mL |
| 10 mM | 0.225 mL | 1.1248 mL | 2.2496 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 | ||||||||||
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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。
Evaluating Vibegron for the treatment of overactive bladder
Expert Opin Pharmacother 2021 Jan;22(1):9-17.PMID:32993398DOI:10.1080/14656566.2020.1809652.
Introduction: Vibegron is a very selective new β3-adrenergic receptor agonist introduced recently to clinical practice for OAB patients, which offers an alternative option for to antimuscarinic drugs. Areas covered: This review presents the current knowledge concerning the mechanism of action, pharmacokinetics, and pharmacodynamics of Vibegron. Moreover, it presents an overview of preclinical and phase II and phase III clinical studies on the efficacy, tolerability, and safety of this agent in patients suffering from OAB. Expert opinion: Clinical studies confirmed efficacy and safety of Vibegron in OAB patients. Vibegron differ from well-known mirabegron with regards to its pharmacological profile because it is metabolized independently from CYP3A4, 2D6, or 2C9 and therefore is less likely to cause a drug-drug interaction. Moreover, since this drug does not penetrate the blood-brain barrier, it could become the drug of choice in OAB patients with cognitive impairment. These properties have paved the way in near future for better-tailored treatments for OAB patients.
Efficacy of Vibegron and Mirabegron for Overactive Bladder: A Systematic Literature Review and Indirect Treatment Comparison
Adv Ther 2021 Nov;38(11):5452-5464.PMID:34537953DOI:10.1007/s12325-021-01902-8.
Background: In the absence of head-to-head trials, we performed an indirect treatment comparison of the β3-adrenergic agonists Vibegron and mirabegron in the treatment of overactive bladder (OAB). Methods: PubMed, Embase, and Cochrane Library were searched for articles related to phase 3, double-blind, controlled trials of Vibegron 75 mg and mirabegron 25/50 mg in patients with OAB. Efficacy outcomes included change from baseline at weeks 4, 12, and 52 in mean daily number of total urinary incontinence episodes and micturitions and mean volume voided/micturition. Effect size was computed as placebo-subtracted change from baseline (weeks 4, 12) or active control (tolterodine)-subtracted change from baseline (week 52) for each treatment group. Adverse events (AEs) are presented descriptively. Results: After removal of duplicates, 49 records were identified, and after screening 9 met inclusion criteria for analysis. Vibegron showed significantly greater reduction in mean daily number of total incontinence episodes than mirabegron 25 mg at week 4, mirabegron 50 mg (weeks 4, 52), and tolterodine (weeks 4, 12) (P < 0.05, each) and significantly greater improvement in volume voided versus mirabegron 25 mg (week 12), mirabegron 50 mg (weeks 12, 52), and tolterodine (week 4) (P < 0.05, each). Confidence intervals of point estimates overlapped zero for all other comparisons of Vibegron and mirabegron (25 or 50 mg) or tolterodine, indicating no significant differences between treatments for these time/endpoints. Urinary tract infection, hypertension, and dry mouth were the most commonly occurring AEs for Vibegron, mirabegron, and tolterodine, respectively, in the short-term trials; hypertension was the most commonly occurring AE with all three treatments in the long-term trials. Conclusions: Vibegron was associated with significant improvement in total incontinence episodes versus mirabegron at 4 and 52 weeks and volume voided at 12 and 52 weeks. Improvement in micturitions was similar between Vibegron and mirabegron or tolterodine. Incidence of AEs was generally comparable between Vibegron and mirabegron.
International Phase III, Randomized, Double-Blind, Placebo and Active Controlled Study to Evaluate the Safety and Efficacy of Vibegron in Patients with Symptoms of Overactive Bladder: EMPOWUR
J Urol 2020 Aug;204(2):316-324.PMID:32068484DOI:10.1097/JU.0000000000000807.
Purpose: We assessed efficacy, safety and tolerability of Vibegron, a novel, potent, highly selective β3-adrenoceptor agonist, administered 12 weeks at 75 mg once daily to patients with overactive bladder in an international phase III trial with placebo and active control. Materials and methods: Adult patients with overactive bladder with 8.0 or more micturitions per day were randomized 5:5:4 to 75 mg Vibegron, placebo or extended-release 4 mg extended-release tolterodine. Up to 25% of patients could have dry overactive bladder (less than 1.0 urge incontinence episode per day). Patients completed 7-day voiding diaries at baseline and weeks 2, 4, 8 and 12. Results: Of 1,518 randomized patients 90.4% completed the trial. At 12 weeks micturitions decreased by an adjusted mean of 1.8 episodes per day for Vibegron vs 1.3 for placebo (p <0.001, co-primary end point) and 1.6 for tolterodine. Among incontinent patients urge incontinence episodes decreased by an adjusted mean 2.0 episodes per day for Vibegron vs 1.4 for placebo (p <0.0001, co-primary end point) and 1.8 for tolterodine. Moreover, Vibegron was statistically significantly superior to placebo for key secondary measures of number of urgency episodes, volume per micturition and proportion of incontinent patients with a 75% or greater reduction in urge incontinence episodes (all p <0.01). Among Vibegron treated patients 1.7% discontinued treatment because of adverse events vs 1.1% for placebo and 3.3% for tolterodine. Incidence of hypertension was 1.7% for Vibegron and for placebo. Conclusions: Once daily 75 mg Vibegron provided statistically significant reductions in micturitions, urgency episodes and urge incontinence, and increased the volume per micturition. Treatment was well tolerated with a favorable safety profile.
Once-Daily Vibegron 75 mg for Overactive Bladder: Long-Term Safety and Efficacy from a Double-Blind Extension Study of the International Phase 3 Trial (EMPOWUR)
J Urol 2021 May;205(5):1421-1429.PMID:33356445DOI:10.1097/JU.0000000000001574.
Purpose: The long-term safety, tolerability and efficacy of Vibegron in adults with overactive bladder were evaluated in the 40-week phase 3 EMPOWUR extension study. Materials and methods: Patients who completed 12 weeks of once-daily Vibegron 75 mg or tolterodine 4 mg extended release in EMPOWUR continued double-blind treatment; patients who completed 12 weeks of placebo were randomly assigned 1:1 to receive double-blind Vibegron or tolterodine. The primary outcome was safety, measured by incidence of adverse events. Secondary outcomes included change from baseline at week 52 in average daily number of micturitions and urgency episodes (all patients), and urge and total urinary incontinence episodes (patients with overactive bladder wet) based on 7-day diary data. Results: Of 506 patients randomized 505 received ≥1 dose of medication, and 430 (85%) completed the study. A total of 12 patients (2.4%) discontinued owing to adverse events. The most common adverse events with Vibegron/tolterodine (>5% in either group) were hypertension (8.8%/8.6%), urinary tract infection (6.6%/7.3%), headache (5.5%/3.9%), nasopharyngitis (4.8%/5.2%) and dry mouth (1.8%/5.2%). Improvements in efficacy end points were maintained for patients receiving Vibegron for 52 weeks; least squares mean change from baseline to week 52 in micturitions was ‒2.4 for Vibegron vs ‒2.0 for tolterodine; in urge urinary incontinence episodes ‒2.2 vs ‒1.7 (p <0.05); in urgency episodes ‒3.4 vs ‒3.2; and in total incontinence episodes ‒2.5 vs ‒1.9 (p <0.05). Among patients with overactive bladder wet 61.0% receiving Vibegron experienced ≥75% reduction in urge urinary incontinence episodes after 52 weeks of treatment vs 54.4% with tolterodine, while 40.8% vs 34.2% experienced a 100% reduction. Conclusions: Vibegron demonstrated favorable long-term safety, tolerability and efficacy in patients with overactive bladder, consistent with results of the 12-week study.
An Evaluation of the Efficacy and Safety of Vibegron in the Treatment of Overactive Bladder
Ther Clin Risk Manag 2022 Mar 3;18:171-182.PMID:35264853DOI:10.2147/TCRM.S310371.
Pharmacologic treatment for overactive bladder (OAB), which is characterized by bothersome symptoms such as urgency and urge urinary incontinence (UUI), includes anticholinergics and β3-adrenergic receptor agonists. Anticholinergics are associated with adverse effects including dry mouth, constipation, cognitive impairment, and increased risk of dementia. Therefore, the drug class of β3-adrenergic receptor agonists may represent an effective, safe treatment option. Vibegron, a β3-adrenergic receptor agonist, was approved for use in Japan (2018) and the United States (2020). Over the past 3 years, 2 phase 3 trials (EMPOWUR, EMPOWUR extension) have been conducted with once-daily Vibegron 75 mg for the treatment of OAB, and additional secondary and subgroup analyses have detailed the efficacy and safety of Vibegron. In the international phase 3 EMPOWUR trial, treatment with Vibegron was associated with significant improvements compared with placebo in efficacy outcomes of micturition frequency, UUI episodes, urgency episodes, and volume voided as early as week 2 that were sustained throughout the 12-week trial. The 40-week EMPOWUR extension study, following the 12-week treatment period, demonstrated sustained efficacy in patients receiving Vibegron for 52 weeks. Treatment with Vibegron was also associated with improvements in patient-reported measures of quality of life. Across studies, Vibegron was generally safe and well tolerated. A separate, dedicated ambulatory blood pressure monitoring study showed that treatment with Vibegron was not associated with clinically meaningful effects on blood pressure or heart rate. Across all studies, Vibegron was efficacious, safe, and well tolerated and thus represents a valuable treatment option for patients with OAB. Here, nearly 1 year after US approval, we review the published data on efficacy and safety of Vibegron 75 mg for the treatment of OAB.