Apraglutide
(Synonyms: FE 203799) 目录号 : GC34473
Apraglutide (FE 203799) is a potent and highly selective GLP-2 agonist with EC50s of 0.03 nM and 0.07 nM for hGLP-2 Receptor and rGLP-2 Receptor, respectively.
Cas No.:1295353-98-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Apraglutide (FE 203799) is a potent and highly selective GLP-2 agonist with EC50s of 0.03 nM and 0.07 nM for hGLP-2 Receptor and rGLP-2 Receptor, respectively.
[1] Diane M Hargrove, et al. J Pharmacol Exp Ther. 2020 May;373(2):193-203.
| Cas No. | 1295353-98-8 | SDF | |
| 别名 | FE 203799 | ||
| 分子式 | C172H263N43O52 | 分子量 | 3765.25 |
| 溶解度 | DMSO : 100 mg/mL (26.56 mM; Need ultrasonic) | 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。 |
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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 | 0.2656 mL | 1.3279 mL | 2.6559 mL |
| 5 mM | 0.0531 mL | 0.2656 mL | 0.5312 mL |
| 10 mM | 0.0266 mL | 0.1328 mL | 0.2656 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 | ||||||||||
| 计算重置 | ||||||||||
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。
Apraglutide, a novel glucagon-like peptide-2 analog, improves fluid absorption in patients with short bowel syndrome intestinal failure: Findings from a placebo-controlled, randomized phase 2 trial
JPEN J Parenter Enteral Nutr 2022 May;46(4):896-904.PMID:34287970DOI:10.1002/jpen.2223.
Background: Treatment with glucagon-like peptide-2 (GLP-2) analogs improve intestinal adaptation in patients with short bowel syndrome-associated intestinal failure (SBS-IF) and may reduce parenteral support requirements. Apraglutide is a novel, long-acting GLP-2 analog designed for once-weekly dosing. This trial investigated the safety and efficacy of Apraglutide in patients with SBS-IF. Methods: In this placebo-controlled, double-blind, randomized, crossover phase 2 trial, eight adults with SBS-IF were treated with once-weekly 5-mg Apraglutide doses and placebo for 4 weeks, followed by once-weekly 10-mg Apraglutide doses for 4 weeks, with a washout period of 6-10 weeks between treatments. Safety was the primary end point. Secondary end points included changes from baseline in urine volume output compared with placebo, collected for 48 h before and after each treatment period. Results: Common treatment-related adverse events (AEs) were mild to moderate and included polyuria, decreased stoma output, stoma complications, decreased thirst, and edema. No serious AEs were considered to be related to Apraglutide treatment. The safety profile was comparable for the lower and higher doses. Treatment with once-weekly 5- and 10-mg Apraglutide doses significantly increased urine volume output by an adjusted mean of 714 ml/day (95% CI, 490-939; P < .05) and 795 ml/day (95% CI, 195-1394; P < .05), respectively, compared with placebo, with no significant differences between doses. Conclusions: Once-weekly Apraglutide was well tolerated at both tested doses and significantly increased urine volume output, providing evidence for increased intestinal fluid absorption. A phase 3 trial is underway in adults with SBS-IF.
Apraglutide, a novel once-weekly glucagon-like peptide-2 analog, improves intestinal fluid and energy absorption in patients with short bowel syndrome: An open-label phase 1 and 2 metabolic balance trial
JPEN J Parenter Enteral Nutr 2022 Sep;46(7):1639-1649.PMID:35233802DOI:10.1002/jpen.2362.
Background: Apraglutide is a novel long-acting glucagon-like peptide-2 (GLP-2) analog designed for once-weekly subcutaneous dosing, with the potential to increase fluid and nutrient absorption by the remnant intestine of patients who have short bowel syndrome (SBS) with intestinal insufficiency (SBS-II) or intestinal failure (SBS-IF). This trial investigated the safety and effects on intestinal absorption of Apraglutide in patients with SBS-II and SBS-IF. Methods: In this open-label, phase 1 and 2 trial, adult patients with SBS-II (n = 4) or SBS-IF (n = 4) and a fecal output of ≥1500 g/day received once-weekly subcutaneous 5 mg Apraglutide for 4 weeks. Safety was the primary end point. Secondary end points included change from baseline in intestinal absorption of wet weight (indicative of fluid absorption), electrolytes, and energy (by bomb calorimetry) measured by inpatient metabolic balance studies. Results: Common treatment-related adverse events were decreased gastrointestinal (GI) stoma output (n = 6), stoma complications (n = 6), GI stoma complications (n = 5), nausea (n = 5), flatulence (n = 4), abnormal GI stoma output (n = 4), polyuria (n = 3), and abdominal pain (n = 3). The only treatment-related serious adverse event (experienced in one patient) was abdominal pain. Apraglutide significantly increased wet weight and energy absorption by an adjusted mean of 741 g/day (95% CI, 194 to 1287; P = 0.015) and 1095 kJ/day (95% CI, 196 to 1994; P = 0.024), respectively. Sodium and potassium absorption significantly increased by an adjusted mean of 38 mmol/day (95% CI, 3 to 74; P = 0.039) and 18 mmol/day (95% CI, 4 to 32; P = 0.020), respectively. Conclusion: Once-weekly 5 mg Apraglutide was well tolerated in patients with SBS-II and SBS-IF and significantly improved the absorption of fluids, electrolytes, and energy.
Pharmacological Characterization of Apraglutide, a Novel Long-Acting Peptidic Glucagon-Like Peptide-2 Agonist, for the Treatment of Short Bowel Syndrome
J Pharmacol Exp Ther 2020 May;373(2):193-203.PMID:32075870DOI:10.1124/jpet.119.262238.
Glucagon-like peptide-2 (GLP-2) agonists have therapeutic potential in clinical indications in which the integrity or absorptive function of the intestinal mucosa is compromised, such as in short bowel syndrome (SBS). Native hGLP-2, a 33-amino acid peptide secreted from the small intestine, contributes to nutritional absorption but has a very short half-life because of enzymatic cleavage and renal clearance and thus is of limited therapeutic value. The GLP-2 analog teduglutide (Revestive/Gattex; Shire Inc.) has been approved for use in SBS since 2012 but has a once-daily injection regimen. Pharmacokinetic (PK) and pharmacodynamic studies confirm that Apraglutide, a novel GLP-2 analog, has very low clearance, long elimination half-life, and high plasma protein binding compared with GLP-2 analogs teduglutide and glepaglutide. Apraglutide and teduglutide retain potency and selectivity at the GLP-2 receptor comparable to native hGLP-2, whereas glepaglutide was less potent and less selective. In rat intravenous PK studies, hGLP-2, teduglutide, glepaglutide, and Apraglutide had clearances of 25, 9.9, 2.8, and 0.27 ml/kg per minute, respectively, and elimination half-lives of 6.4, 19, 16, and 159 minutes, respectively. The unique PK profile of Apraglutide administered via intravenous and subcutaneous routes was confirmed in monkey and minipig and translated into significantly greater in vivo pharmacodynamic activity, measured as small intestinal growth in rats. Apraglutide showed greater intestinotrophic activity than the other peptides when administered at less-frequent dosing intervals because of its prolonged half-life. We postulate that Apraglutide offers several advantages over existing GLP-2 analogs and is an excellent candidate for the treatment of gastrointestinal diseases, such as SBS. SIGNIFICANCE STATEMENT: Apraglutide is a potent and selective GLP-2 agonist with an extremely low clearance and prolonged elimination half-life, which differentiates it from teduglutide (the only approved GLP-2 agonist). The enhanced pharmacokinetics of Apraglutide will benefit patients by enabling a reduced dosing frequency and removing the need for daily injections.
Site-Specific and Temporal Effects of Apraglutide, a Novel Long-Acting Glucagon-Like Peptide-2 Receptor Agonist, on Intestinal Growth in Mice
J Pharmacol Exp Ther 2020 Jun;373(3):347-352.PMID:32144124DOI:10.1124/jpet.119.263947.
Long-acting glucagon-like peptide-2 receptor (GLP-2R) agonists are well-established to increase intestinal growth in rodents and, most notably, humans with short bowel syndrome. Most of the trophic effects of GLP-2R agonists are reported to be mediated through increased growth of the crypt-villus axis, resulting in enhanced mucosal mass and improved intestinal function. The present study examined the effects of Apraglutide, a novel GLP-2R agonist, on the growth of the small intestine and colon after 3, 7, and 10 weeks of treatment in male and female mice. Apraglutide (3 mg/kg; three times per week) significantly increased small intestinal weight (P < 0.001) and length (P < 0.001) after 3 weeks of administration, with a further increase in effectiveness after 10 weeks (P < 0.01). Crypt depth and villus height were both markedly increased after 3 weeks of Apraglutide administration (P < 0.001) but did not show any further increase with duration of treatment, whereas crypt number and intestinal circumference were increased after 7 and 10 weeks (P < 0.01) but not after 3 weeks of Apraglutide treatment. Both the weight and the length of the colon were also enhanced by Apraglutide treatment for 3 weeks (P < 0.001), and these effects were maintained but did not improve further with continued Apraglutide administration. The results of this study demonstrate that the novel, long-acting GLP-2R agonist, Apraglutide, demonstrates an unexpected marked ability to increase intestinal length as well as exert time- and location-dependent specificity in its intestinotrophic actions. SIGNIFICANCE STATEMENT: The novel long-acting glucagon-like peptide 2 receptor agonist, Apraglutide, enhances intestinal weight as well as intestinal length in a time- and site-dependent fashion.
Novel Long-Acting GLP-2 Analogue, FE 203799 (Apraglutide), Enhances Adaptation and Linear Intestinal Growth in a Neonatal Piglet Model of Short Bowel Syndrome with Total Resection of the Ileum
JPEN J Parenter Enteral Nutr 2019 Sep;43(7):891-898.PMID:30614011DOI:10.1002/jpen.1500.
Background: Glucagon-like peptide-2 (GLP-2) is an intestinotrophic factor released from L-cells in the ileum, a segment commonly resected or atretic in neonatal short bowel syndrome (SBS). In piglets, ileal resection decreases intestinal adaptation and endogenous GLP-2 production, whereas exogenous replacement promotes adaptation. In this study, we determined the effect of a novel long-acting GLP-2 analogue, FE 203799 (FE; Apraglutide), upon intestinal growth, adaptation, and function in neonatal SBS piglets without ileum. Methods: Neonatal piglets were randomized to saline (n = 10) vs FE treatment (n = 8). All piglets underwent 75% intestinal resection with jejunocolic anastomosis and were pair-fed parenteral and enteral nutrition. Saline and FE (5 mg/kg) treatments were administered subcutaneously on days 0 and 4. On day 6, 24-hour fecal samples were collected for subsequent nutrient analysis. On day 7, small-intestinal length and weight were measured and tissue collected for analyses. Results: On day 7, saline and FE-treated piglets were healthy and gained equivalent weight (P = 0.12). Compared with saline piglets, FE-treated piglets had lower fecal fat (P = 0.043) and energy (P = 0.043) losses and exhibited intestinal lengthening (P = 0.001), greater small-intestinal weight (P = 0.004), longer villus height (P = 0.027), and greater crypt depth (P = 0.054). Conclusions: The subcutaneous GLP-2 analogue, FE, enhanced intestinal adaptation in a neonatal model of SBS without ileum. The observed intestinal lengthening with FE treatment was unique compared with our prior experience with native GLP-2 in this same model and has important clinical implications for treating neonatal SBS. At this developmental stage, growth in the intestine, if augmented, could accelerate weaning from parenteral nutrition.