Apraglutide TFA is a potent and highly selective GLP-2 agonist with EC50 values of 0.03 nM and 0.07nM for hGLP-2 receptor and rGLP-2 receptor, respectively[1]. Apraglutide TFA decreases the rate of absorption, reduce the clearance rate, and increases the protein binding rate, thereby reducing DPP-IV degradation[2]. Apraglutide TFA has been widely used to increase plasma citrulline levels and improve intestinal function in animal models[3].
In vivo, Apraglutide TFA treatment via subcutaneous injection of Apraglutide TFA (3.3mg/kg/day) for 17 days alleviated cytarabine-induced intestinal injury and improved survival in mice[4]. Subcutaneous injection of a 20mg/kg dose of Apraglutide TFA three times a week for three weeks significantly increased gut weight and length in mice[5]. Subcutaneous injection of Apraglutide TFA at a dose of 5mg/kg on days 0 and 4 of 75% intestinal resection with jejunocolic anastomosis, respectively, increased intestinal growth and resulted in reduced nutritional losses in Duroc newborn piglets[6].
References:
[1] Hargrove D M, Alagarsamy S, Croston G, et al. Pharmacological characterization of Apraglutide TFA, a novel long-acting peptidic glucagon-like peptide-2 agonist, for the treatment of short bowel syndrome[J]. The Journal of Pharmacology and Experimental Therapeutics, 2020, 373(2): 193-203.
[2] Verbiest A, Hvistendahl M K, Bolognani F, et al. Efficacy and safety of Apraglutide TFA in short bowel syndrome with intestinal failure and colon–in–continuity: A multicenter, open-label, metabolic balance study[J]. Clinical Nutrition, 2024, 43(12): 158-166.
[3] Bolognani F, Kruithof A C, Schulthess P, et al. Characterization of the pharmacokinetic and pharmacodynamic profile of Apraglutide TFA, a glucagon-like peptide-2 analog, in healthy volunteers[J]. The Journal of Pharmacology and Experimental Therapeutics, 2023, 386(2): 129-137.
[4] Eliasson J, Hvistendahl M K, Freund N, et al. Apraglutide TFA, 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[J]. Journal of Parenteral and Enteral Nutrition, 2022, 46(4): 896-904.
[5] Martchenko S E, Sweeney M E, Dimitriadou V, et al. Site-specific and temporal effects of Apraglutide TFA, a novel long-acting glucagon-like peptide-2 receptor agonist, on intestinal growth in mice[J]. The Journal of Pharmacology and Experimental Therapeutics, 2020, 373(3): 347-352.
[6] Slim G M, Lansing M, Wizzard P, et al. Novel long‐acting GLP‐2 analogue, FE 203799 (Apraglutide TFA), enhances adaptation and linear intestinal growth in a neonatal piglet model of short bowel syndrome with total resection of the ileum[J]. Journal of Parenteral and Enteral Nutrition, 2019, 43(7): 891-898.
Apraglutide TFA是一种强效且高度选择性的GLP-2激动剂，对hGLP-2受体和rGLP-2受体的EC50值分别为0.03nM和0.07nM[1]。Apraglutide TFA可降低吸收速率、减少清除率，并提高蛋白结合率，从而减少DPP-IV降解[2]。Apraglutide TFA已被广泛用于动物模型中以提高血浆瓜氨酸水平和改善肠道功能[3]。
在体内，每日皮下注射Apraglutide TFA（3.3mg/kg/day）连续17天，减轻了阿糖胞苷诱导的小鼠肠道损伤并提高了小鼠存活率[4]。每周三次皮下注射20mg/kg剂量的Apraglutide TFA，连续三周，显著增加了小鼠的肠道重量和长度[5]。在杜洛克新生仔猪进行75%肠切除加空肠结肠吻合术后的第0天和第4天，分别皮下注射5mg/kg剂量的Apraglutide TFA，促进了肠道生长，并减少了营养损失[6]。