Trofinetide (NNZ-2566)是内源性N末端三肽甘氨酸-脯氨酸-谷氨酸（GPE）的合成类似物，具有神经保护作用。
Cas No.:853400-76-7
Sample solution is provided at 25 µL, 10mM.
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Trofinetide (NNZ-2566) is a synthetic analogue of the endogenous N-terminal tripeptide Glycine Proline-Glutamate (GPE) with neuroprotective effects [1]. Trofinetide can cross the blood-brain barrier and improve synaptic function, repair synaptic structure, reduce neuroinflammatory substances in the brain, and enhance antioxidant response[2]. Trofinetide has been widely used in Fmr1 knockout mice to correct learning and memory deficits, abnormal hyperactivity, and social interaction impairments [3].
In vitro, Trofinetide pretreatment at 1μM for 2 hours effectively reversed the cytotoxicity of Aβ42 (10µM; 24h) on BV2 cells and increased cell viability[4]. Treatment with 10μM Trofinetide for 24h reversed okadaic acid-induced cell death in isolated embryonic striatal neurons[5].
In vivo, Trofinetide treatment via continuous intravenous infusion at a rate of 3mg/kg/h for 12 hours inhibited neuroinflammation and proinflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats[6]. Intravenous infusion of Trofinetide (10mg/kg/h) for 4 hours significantly reduced infarct size in rats caused by middle cerebral artery occlusion (MCAO) and attenuated weight loss[7].
References:
[1] Neul J L, Percy A K, Benke T A, et al. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study[J]. Nature Medicine, 2023, 29(6): 1468-1475.
[2] Hudu S A, Elmigdadi F, Qtaitat A A, et al. Trofinetide for Rett syndrome: highlights on the development and related inventions of the first USFDA-approved treatment for rare pediatric unmet medical need[J]. Journal of Clinical Medicine, 2023, 12(15): 5114.
[3] Deacon R M J, Glass L, Snape M, et al. NNZ-2566, a novel analog of (1–3) IGF-1, as a potential therapeutic agent for fragile X syndrome[J]. Neuromolecular medicine, 2015, 17(1): 71-82.
[4] Chen M, Ning Y, Yang H, et al. Trofinetide Improves Cognitive Function in APP/PS1 Mice by Suppressing Inflammation and Apoptosis[J]. Molecular Neurobiology, 2026, 63(1): 129.
[5] Bickerdike M J, Thomas G B, Batchelor D C, et al. NNZ-2566: A Gly–Pro–Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke[J]. Journal of the neurological sciences, 2009, 278(1-2): 85-90.
[6] Wei H H, Lu X C M, Shear D A, et al. NNZ-2566 treatment inhibits neuroinflammation and pro-inflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats[J]. Journal of neuroinflammation, 2009, 6(1): 19.
[7] Bickerdike M J, Thomas G B, Batchelor D C, et al. NNZ-2566: A Gly–Pro–Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke[J]. Journal of the neurological sciences, 2009, 278(1-2): 85-90.
Trofinetide (NNZ-2566)是内源性N末端三肽甘氨酸-脯氨酸-谷氨酸（GPE）的合成类似物，具有神经保护作用[1]。Trofinetide能够穿越血脑屏障，改善突触功能，修复突触结构，降低脑内神经炎症物质，并增强抗氧化反应[2]。Trofinetide已被广泛用于Fmr1基因敲除小鼠，以纠正学习和记忆缺陷、异常多动以及社交互动障碍[3]。
在体外，使用1μM的Trofinetide预处理BV2细胞2小时，有效逆转了Aβ42（10μM；24小时）诱导的细胞毒性，并提高了细胞活力[4]。使用10μM的Trofinetide处理分离的胚胎纹状体神经元24小时，逆转了okadaic acid诱导的细胞死亡[5]。
在体内，以3mg/kg/h的速率连续静脉输注Trofinetide 12小时，抑制了实验性穿透性弹道样脑损伤诱导的大鼠神经炎症和促炎细胞因子表达[6]。静脉输注Trofinetide（10mg/kg/h）4小时，显著减小了大脑中动脉闭塞（MCAO）引起的大鼠梗死面积，并减轻了体重下降[7]。
| Cell experiment [1]: | |
Cell lines | BV2 cells |
Preparation Method | BV2 cells were cultured in DMEM supplemented with 10% fetal bovine serum (FBS) at 37°C in 5% CO2. Cells were plated onto a 96-well plate at a density of 3×103 cells/ml for 24h, and the cells were incubated with different concentrations of Trofinetide 1µM for 2h, followed by co-incubation with Aβ42 oligomers (10µM) for an additional 24h. After 72 hours, cell viability was analyzed. |
Reaction Conditions | 1µM; 2h |
Applications | Trofinetide pretreatment significantly rescued Aβ42-induced cytotoxicity in BV2 cells. |
| Animal experiment [2]: | |
Animal models | Male Sprague-Dawley rats |
Preparation Method | Male Sprague-Dawley rats were weighed and anaesthetized with 5% halothane/O2 and maintained with 3% halothane/O2 throughout surgery. A blunt 22G×8.5mm guide cannula was stereotaxically implanted and rested on the dura, positioned to enable an injection cannula to be lowered adjacent to the middle cerebral artery (0.2mm anterior, 5.2mm lateral to Bregma) and was anchored in place with dental cement. To enable intravenous (i.v.) infusion of Trofinetide, rats were surgically fitted with an indwelling catheter into the jugular vein and housed individually in metabolic cages before induction of the stroke-like injury. Three to four days following surgery, a stroke-like injury was induced. A 15.8mm 30G needle connected to a 1ml syringe with polythene tubing was inserted into the guide cannula, and ET-1 (100pmol in 3µl) was infused over a period of approximately 3min to induce vasoconstriction of the middle cerebral artery. Following stroke injury, Trofinetide or vehicle was administered intravenously via the indwelling catheter (10mg/kg/h for 4h, starting 3h after stroke). Five days following drug treatment, rats were sacrificed, and the brains were taken for histological analysis. |
Dosage form | 30mg/kg/h for 4h; i.v. |
Applications | Trofinetide treatment reduced brain injury size in rats subjected to focal stroke. |
References: | |
| Cas No. | 853400-76-7 | SDF | |
| 别名 | NNZ-2566 | ||
| Canonical SMILES | O=C(O)CC[C@@H](C(O)=O)NC([C@@]1(C)N(C(CN)=O)CCC1)=O | ||
| 分子式 | C13H21N3O6 | 分子量 | 315.32 |
| 溶解度 | Water : ≥ 50 mg/mL (158.57 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。 |
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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 | 3.1714 mL | 15.8569 mL | 31.7138 mL |
| 5 mM | 634.3 μL | 3.1714 mL | 6.3428 mL |
| 10 mM | 317.1 μL | 1.5857 mL | 3.1714 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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2.
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