Survodutide (BI 456906) is a synthetic 29-amino-acid peptide designed as a dual agonist targeting both the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R). It incorporates structural modifications to the human glucagon sequence, including a non-coded amino acid (1-aminocyclobutane-1-carboxylic acid) at position 2 to enhance proteolytic stability and a glycine-serine linker at position 24 with a C18 fatty acid moiety to prolong half-life through albumin binding. In vitro assays demonstrate that BI 456906 acts as a potent agonist at both receptors, with functional potencies in the nanomolar range for human GCGR and GLP-1R. The peptide exhibits balanced dual receptor engagement, as confirmed in cellular models and transgenic reporter systems, where it simultaneously activates signaling pathways in tissues expressing these receptors.

This peptide is administered via subcutaneous injection and exhibits a long-acting profile. Its dual receptor engagement enables synergistic mechanisms that influence metabolic pathways, including regulation of insulin and glucagon secretion, inhibition of food intake, and modulation of gastric emptying.

• Zimmermann T, Thomas L, Baader-Pagler T, Haebel P, Simon E, Reindl W, Bajrami B, Rist W, Uphues I, Drucker DJ, Klein H, Santhanam R, Hamprecht D, Neubauer H, Augustin R. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Mol Metab. 2022 Dec;66:101633. doi: 10.1016/j.molmet.2022.101633. Epub 2022 Nov 7. PMID: 36356832; PMCID: PMC9679702.
• Awad AA, Abdrabou Abouelmagd A, Mohammed F, Elettreby AM, Mahmoud Marey M, Aldemerdash MA, Soliman SM, Belal MM, Abosheaishaa H. Evaluating the efficacy and safety of survodutide for obesity: a systematic review and meta-analysis of randomized controlled trials. Proc (Bayl Univ Med Cent). 2025 Apr 1;38(4):514-522. doi: 10.1080/08998280.2025.2480512. PMID: 40557198; PMCID: PMC12184113.

三氟乙酸（Trifluoroacetic acid，简称 TFA）是高效液相色谱（简称 HPLC）纯化过程中常用的反离子。TFA 的存在可能会对肽的净重量、外观及溶解度产生影响，具体如下：

对净重量的影响：TFA 盐会增加产物的总质量。在大多数情况下，肽的含量占总重量的 80% 以上，剩余部分则为 TFA。

对溶解度的影响：TFA 盐通常能提高肽在水溶液中的溶解度。

在生物检测中的影响：对于大多数标准的体外检测，残留的 TFA 水平一般不会造成干扰。但需注意，在高灵敏度的细胞研究或生化研究中，需关注其存在可能带来的影响。

干品多肽的重量中不仅仅包含多肽，还包含有一些非肽的组份，如水、被吸收的溶剂、配位离子和盐等。肽的净含量是指肽在其中的重量百分比，这个百分比的数值范围很大，可能从50%到90%，取决于纯度、序列以及合成和纯化的方法，不要将肽的净含量和肽的纯度混为一谈，他们是两个完全不同的概念。纯度通常是通过HPLC测定的。纯度定义的是多肽样品中含正确序列的组分的百分比，而肽的净含量是指样品中肽类物质相对于总物质所占的百分比，肽的净含量通常是氨基酸组分分析或紫外分光法测定的，这个信息主要是在一些对肽的浓度很敏感的实验中，对计算肽的浓度是很重要的。