Home>>Signaling Pathways>> GPCR/G protein>> GHSR>>AZP-531

AZP-531 Sale

目录号 : GC31430

AZP-531是一种用于提高血糖控制并减轻体重的非格酸化生长素释放肽类似物。

AZP-531 Chemical Structure

Cas No.:1088543-62-7

规格 价格 库存 购买数量
1mg
¥1,071.00
现货
5mg
¥4,284.00
现货
10mg
¥6,962.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Animal experiment:

Rats: AZP-531 is administered in sterile water to obtain a 1 mg/kg and 0.3 mg/kg dose in the rat through both intravenous and subcutaneous routes. Blood is collected at t=0, 2, 5, 15, 30, 60, 120, 240, 360, 480 and 1440 min post-administration for the intravenous dose route and t=0, 15, 30, 60, 120, 240, 360, 480 and 1440 min post-administration for the subcutaneous route[1]. Mice: AZP531 is prepared in saline. C57BL/6J mice are infused with saline, DAG, or AZP531 continuously for 4 weeks, and fed either normal diet (ND) or normal diet for 2 weeks followed by a high-fat diet (HFD) for 2 weeks. Peptides are infused at 4 nM/kg/h[2].

References:

[1]. Julien M, et al. In vitro and in vivo stability and pharmacokinetic profile of unacylated ghrelin (UAG) analogues. Eur J Pharm Sci. 2012 Nov 20;47(4):625-35.
[2]. Delhanty PJ, et al. Des-acyl ghrelin analogs prevent high-fat-diet-induced dysregulation of glucosehomeostasis. FASEB J. 2013 Apr;27(4):1690-700.
[3]. Allas S, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of AZP-531, a first-in-class analogue of unacylated ghrelin, in healthy and overweight/obese subjects and subjects with type 2 diabetes. Diabetes Obes Metab. 2016 Sep;18(9):868-74.

产品描述

AZP-531 is an analogue of unacylated ghrelin designed to improve glycaemic control and reduce weight.

AZP-531 exerts survival effects on pancreatic b-cells and human pancreatic islets which is comparable to that of UAG, the parent molecule. AZP-531 is very stable in human plasma in vitro. No degradation is observed after 1 day of incubation at 37°C[1].

The highest concentration of this peptide is 4350 ng/mL, and the majority of samples are above the limit of quantification (1 ng/mL)[1]. AZP-531 infusion prevents the increase in body weight caused by high-fat diet in mice. AZP-531 treatment prevents high-fat diet-induced proinflammatory effects, stimulates expression of mitochondrial function markers in brown adipose tissue, and prevents development of a prediabetic metabolic state. AZP-531 also prevents a high-fat diet-induced increase in acyl ghrelin levels[2]. AZP-531 is well tolerated. Single- and multiple-dose pharmokinetic variables are similar. Maximum AZP-531 concentrations are typically reached at 1 h post-dose. Observed maximum concentration and area under the curve are dose-proportional. The mean terminal half-life is 2-3 h. AZP-531 (≥15 μg/kg) significantly improves glucose concentrations, without increasing insulin levels, suggesting an insulin-sensitizing effect. AZP-531 decreases mean body weight by 2.6 kg (vs 0.8 kg for placebo). Glucose variables improve in all groups, including placebo, suggesting a study effect in uncontrolled patients at baseline. AZP-531 60 μg/kg reduces HbA1c by 0.4% (vs 0.2% for placebo) and body weight by 2.1 kg (vs 1.3 kg for placebo)[3].

[1]. Julien M, et al. In vitro and in vivo stability and pharmacokinetic profile of unacylated ghrelin (UAG) analogues. Eur J Pharm Sci. 2012 Nov 20;47(4):625-35. [2]. Delhanty PJ, et al. Des-acyl ghrelin analogs prevent high-fat-diet-induced dysregulation of glucosehomeostasis. FASEB J. 2013 Apr;27(4):1690-700. [3]. Allas S, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of AZP-531, a first-in-class analogue of unacylated ghrelin, in healthy and overweight/obese subjects and subjects with type 2 diabetes. Diabetes Obes Metab. 2016 Sep;18(9):868-74.

Chemical Properties

Cas No. 1088543-62-7 SDF
Canonical SMILES Cyclo(Arg-Val-Gln-Ser-Pro-Glu-His-Gln)
分子式 C40H63N15O13 分子量 962.02
溶解度 DMSO : 100 mg/mL (103.95 mM) 储存条件 Store 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。
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。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 1.0395 mL 5.1974 mL 10.3948 mL
5 mM 0.2079 mL 1.0395 mL 2.079 mL
10 mM 0.1039 mL 0.5197 mL 1.0395 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

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
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

Research Update

AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial

Context and objective: Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available. Methods and design: Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50-70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures. Results: AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion. Conclusions: AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.

Safety, tolerability, pharmacokinetics and pharmacodynamics of AZP-531, a first-in-class analogue of unacylated ghrelin, in healthy and overweight/obese subjects and subjects with type 2 diabetes

Aim: To explore the safety, pharmacokinetics and pharmacodynamics in humans of the unacylated ghrelin analogue AZP-531, designed to improve glycaemic control and reduce weight.
Methods: Assessments, including glucose measurements, were performed in a three-part randomized study. In Part A, healthy subjects [n = 44, age 18-50 years, body mass index (BMI) 20-28 kg/m(2) ] received a single subcutaneous dose of 0.3, 3, 15, 30, 60 or 120 ?g/kg AZP-531 or placebo. In Part B, overweight/obese subjects (n = 32, age 18-65 years, BMI 28-38 kg/m(2) ) and in Part C, patients with type 2 diabetes [T2D; n = 36, age 18-65 years, BMI 20-40 kg/m(2) , glycated haemoglobin (HbA1c) 7-10%] received AZP-531 or placebo for 14 days (daily doses of 3, 15, 30 or 60 ?g/kg and 15, 2 ℅ 30 or 60 ?g/kg, respectively).
Results: AZP-531 was well tolerated. Single- and multiple-dose pharmokinetic variables were similar. Maximum AZP-531 concentrations were typically reached at 1 h post-dose. Observed maximum concentration (Cmax ) and area under the curve were dose-proportional. The mean terminal half-life (t1/2 ) was 2-3 h. In Part B, AZP-531 doses of ≡15 ?g/kg significantly improved glucose concentrations, without increasing insulin levels, suggesting an insulin-sensitizing effect. AZP-531 decreased mean body weight by 2.6 kg (vs 0.8 kg for placebo). In Part C, glucose variables improved in all groups, including placebo, suggesting a study effect in uncontrolled patients at baseline. Notwithstanding, AZP-531 60 ?g/kg reduced HbA1c by 0.4% (vs 0.2% for placebo) and body weight by 2.1 kg (vs 1.3 kg for placebo).
Conclusions: AZP-531 was well tolerated in this first-in-human study. Its pharmacokinetic profile, suitable for once-daily dosing, and metabolic effects support further clinical development for T2D.

Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531

Breast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, remains the second leading cause of cancer-related death. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP-531. We report potent anti-tumor effects of unacylated ghrelin, dependent on cells being cultured in 3D in a biologically-relevant extracellular matrix. The mechanism of unacylated ghrelin-mediated growth inhibition involves activation of G汐i and suppression of MAPK signaling. AZP-531 also suppresses the growth of breast cancer cells in vitro and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer.

Unacylated ghrelin analog prevents myocardial reperfusion injury independently of permeability transition pore

Reperfusion injury is responsible for an important part of myocardial infarct establishment due notably to triggering cardiomyocytes death at the first minutes of reperfusion. AZP-531 is an optimized analog of unacylated ghrelin currently in clinical development in several metabolic diseases. We investigated a potential cardioprotective effect of AZP-531 in ischemia/reperfusion (IR) and the molecular underlying mechanism(s) involved in this protection. In vivo postconditioning with AZP-531 in C57BL6 mouse IR model decreased infarct size. Western blot analysis on areas at risk from the different mouse groups showed that AZP-531 activates Akt, ERK1-2 as well as S6 and 4EBP1, mTORC1 effectors. We also showed an inhibition of caspase 3 cleavage and Bax translocation to the mitochondria. AZP-531 also stimulated the expression of antioxidants and was capable of decreasing mitochondrial H2O2 production, contributing to the reduction of ROS accumulation. AZP-531 exhibits cardioprotective effect when administrated for postconditioning in C57BL6 mouse IR model. Treatment with AZP-531 rescued the myocardium from cell death at early reperfusion by stimulating protein synthesis, inhibiting Bax/caspase 3-induced apoptosis as well as ROS accumulation and oxidative stress-induced necrosis. AZP-531 may prove useful in the treatment of IR injury.

Clinical perspectives for ghrelin-derived therapeutic products

Because of its orexigenic, adipogenic and diabetogenic activities, acylated ghrelin (AG) has emerged as an attractive target for the treatment of obesity and type 2 diabetes. Pharmacological tools have been designed in order to antagonize or block the hormone's activity, or inhibit ghrelin O-acyltransferase (GOAT), the enzyme that catalyzes its acylation. AG antagonists, shown to be potent inhibitors of growth hormone (GH) secretion, were not able to consistently induce the desirable metabolic effects. Some of them, on the contrary, acted as AG agonists. Similarly, AG-blocking agents including Spiegelmers, vaccines, and monoclonal antibodies, gave mixed results. More encouraging yet very preliminary data were obtained with a novel GOAT inhibitor. However, although significant, the observed decrease in circulating AG levels was partial and improvement work remains to be done. Unacylated ghrelin (UAG) and analogs were shown to potently and rapidly inhibit plasma AG levels, and to improve glucose metabolism in addition to displaying beneficial effects on a variety of cells. These data support the rationale for further development of this new therapeutic class in type 2 diabetes and the Prader-Willi syndrome. A development program is underway with AZP-531, a cyclized UAG(6-13) analog with improved pharmacokinetic properties.