Exendin-4
(Synonyms: 艾塞那肽; Exenatide) 目录号 : GC13391
Exendin-4是由39个氨基酸（48-86）组成的多肽，是一种长效的胰高血糖素样肽-1（GLP-1）受体激动剂，IC50为3.22 nM。
Cas No.:141758-74-9
Sample solution is provided at 25 µL, 10mM.
Exendin-4 is a 39-amino-acid polypeptide (48-86) and a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist with an IC50 of 3.22 nM[1]. The mechanism of action of Exendin-4 is by binding to the GLP-1 receptor, activating adenylyl cyclase, increasing intracellular cAMP levels, and ultimately promoting insulin secretion while inhibiting glucagon secretion [2]. Exendin-4 has the effect of lowering blood pressure and inducing aortic vasodilation [3].
In vitro, Exendin-4 (0-20nM) incubated HUVEC cells for 15 minutes, which induced a dose-dependent increase in intracellular cAMP concentration, and Exendin-4 (20nM) increased the production of NO in HUVEC cells and increased p-eNOS and GTPCH1 levels [4]. Exendin-4 (0-10μM) treated MCF-7 cells for 48 hours, which had a significant cytotoxic effect with an IC50 of 5μM and reduced the expression of caspase-9, Akt and MMP2 in the cells [5].
In vivo, exendin-4 (10μg/kg or 20μg/kg) was used to treat obese mice via subcutaneous injection for 60 days, which improved serum ALT, reduced serum glucose and insulin levels, and mice in the low-dose group lost weight. 7%, and the body weight of mice in the high-dose group decreased by 14%[6]. Exendin-4 (10 μg/kg) treated SD rats by subcutaneous injection for 75 days, reduced body weight by approximately 30%, significantly reduced insulin, adiponectin, and leptin levels, but caused pancreatic acinar inflammation and pus toxicosis[7].
References:
[1] Doyle M E, Theodorakis M J, Holloway H W, et al. The importance of the nine-amino acid C-terminal sequence of exendin-4 for binding to the GLP-1 receptor and for biological activity[J]. Regulatory peptides, 2003, 114(2-3): 153-158.
[2] Doyle M E, Egan J M. Mechanisms of action of glucagon-like peptide 1 in the pancreas[J]. Pharmacology & therapeutics, 2007, 113(3): 546-593.
[3] Sélley E, Kun S, Szijártó I A, et al. Exenatide induces aortic vasodilation increasing hydrogen sulphide, carbon monoxide and nitric oxide production[J]. Cardiovascular Diabetology, 2014, 13: 1-9.
[4]Wei R, Ma S, Wang C, et al. Exenatide exerts direct protective effects on endothelial cells through the AMPK/Akt/eNOS pathway in a GLP-1 receptor-dependent manner[J]. American Journal of Physiology-Endocrinology and Metabolism, 2016, 310(11): E947-E957.
[5]Fidan-Yaylalı G, Dodurga Y, Seçme M, et al. Antidiabetic exendin-4 activates apoptotic pathway and inhibits growth of breast cancer cells[J]. Tumor Biology, 2016, 37: 2647-2653.
[6]Ding X, Saxena N K, Lin S, et al. Exendin‐4, a glucagon‐like protein‐1 (GLP‐1) receptor agonist, reverses hepatic steatosis in ob/ob mice[J]. Hepatology, 2006, 43(1): 173-181.
[7]Nachnani J S, Bulchandani D G, Nookala A, et al. Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreas[J]. Diabetologia, 2010, 53: 153-159.
Exendin-4是由39个氨基酸（48-86）组成的多肽，是一种长效的胰高血糖素样肽-1（GLP-1）受体激动剂，IC50为3.22 nM[1]。Exendin-4的作用机制是通过与GLP-1受体结合，激活腺苷酸环化酶，增加细胞内cAMP水平，最终促进胰岛素的分泌，同时抑制胰高血糖素的分泌[2]。Exendin-4具有降低血压，诱导主动脉血管舒张的作用[3]。
在体外，Exendin-4（0-20nM）孵育HUVEC细胞15分钟，诱导了细胞内cAMP浓度呈剂量依赖性增加，且Exendin-4（20nM）增加了HUVEC细胞内NO的产生，升高了p-eNOS和GTPCH1水平[4]。Exendin-4（0-10μM）处理MCF-7细胞48 h，具有显著的细胞毒性作用，IC50为5μM，且降低了细胞中caspase-9、Akt和MMP2的表达[5]。
在体内，Exendin-4（10 μg/kg或20 μg/kg）通过皮下注射治疗肥胖小鼠，持续60天，均改善了血清ALT，降低了血清葡萄糖和胰岛素水平，低剂量组小鼠体重减少7%，高剂量组小鼠体重减少14%[6]。Exendin-4（10μg/kg）通过皮下注射处理SD大鼠，持续75天，体重减轻了约30%，显著降低了胰岛素、脂联素和瘦素水平，但会导致胰腺腺泡炎症和脓毒症[7]。
Cell experiment [1]: | |
Cell lines | HUVEC cell lines |
Preparation method | HUVECs were seeded at a density of 106/dish and incubated overnight for attachment. The cells were incubated with Exendin-4 at various concentrations (0–50nM) for 15 min. |
Reaction Conditions | 0-50 nM ; 15 min |
Applications | Incubation with exendin-4 (≤20nM) for 15 minutes induced a dose-dependent increase in intracellular cAMP concentration. |
Animal experiment [2]: | |
Animal models | ob/ob mice |
Preparation method | The Exendin-4 treated group received 10 μg/kg every 24 hours for the first 14 days. This treatment was the induction phase. After 14 days, the mice treated with Exendin-4 were randomly divided into two groups: one group received a high dose of Exendin-4 (20 μg/kg) every 12 hours; the second group continued to receive a low dose of Exendin-4 (10 μg/kg) every 12 hours. The mice were weighed every day during the 60-day treatment period. |
Dosage form | 10μg/kg、20μg/kg; s.c. |
Applications | Low-dose Exendin-4 treated ob/ob mice sustained a reduction of 7% body weight; high-dose treated animals sustained a net weight reduction of 14%. |
References: [1]Wei R, Ma S, Wang C, et al. Exenatide exerts direct protective effects on endothelial cells through the AMPK/Akt/eNOS pathway in a GLP-1 receptor-dependent manner[J]. American Journal of Physiology-Endocrinology and Metabolism, 2016, 310(11): E947-E957. [2] Ding X, Saxena N K, Lin S, et al. Exendin‐4, a glucagon‐like protein‐1 (GLP‐1) receptor agonist, reverses hepatic steatosis in ob/ob mice[J]. Hepatology, 2006, 43(1): 173-181. | |
| Cas No. | 141758-74-9 | SDF | |
| 别名 | 艾塞那肽; Exenatide | ||
| Canonical SMILES | CCC(C)C(C(=O)NC(CCC(=O)O)C(=O)NC(CC1=CNC2=CC=CC=C21)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(=O)N)C(=O)NCC(=O)NCC(=O)N3CCCC3C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N4CCCC4C(=O)N5CCCC5C(=O)N6CCCC6C(=O)NC(CO)C(=O)N)NC(=O)C(CC7=CC=CC=C7)NC(=O)C(CC(C)C)NC( | ||
| 分子式 | C184H282N50O60S | 分子量 | 4186.57 |
| 溶解度 | ≥ 145 mg/mL in DMSO, ≥ 52 mg/mL in Water with gentle warming | 储存条件 | Store at -20°C,protect from light |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.2389 mL | 1.1943 mL | 2.3886 mL |
| 5 mM | 0.0478 mL | 0.2389 mL | 0.4777 mL |
| 10 mM | 0.0239 mL | 0.1194 mL | 0.2389 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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