Fosgonimeton是一种高度特异性的HGF/MET（肝细胞生长因子/间充质-上皮转化因子受体）神经营养系统的小分子正向调节剂。
Cas No.:2093305-05-4
Sample solution is provided at 25 µL, 10mM.
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Fosgonimeton is a highly specific small-molecule positive modulator of the HGF/MET(Hepatocyte Growth Factor/Mesenchymal-Epithelial Transition) neurotrophic system. Fosgonimeton is a prodrug optimized for subcutaneous (SC) administration and is rapidly converted into the active metabolite fosgo-AM in plasma. Fosgo-AM crosses the blood-brain barrier and enhances the interaction of HGF with its receptor tyrosine kinase MET, inducing downstream signaling through PI3k/Akt and MAPK pathways and augmenting N-methyl-D-aspartate (NMDA) receptor-mediated long-term potentiation through protein kinase C. Fosgonimeton has demonstrated neurotrophic and pro-cognitive effects in preclinical models of dementia[1][2].
In vivo, Subcutaneous administration of Fosgonimeton (0.125, 0.25, 0.5, 1, and 2mg/kg) for 14 days significantly restored cognitive function at all tested doses in Aβ peptide-treated adult male Wistar rats[2]. Subcutaneous administration of Fosgonimeton at doses of 0.25, 0.5, and 1.25mg/kg for 14 consecutive days significantly improved cognitive deficits in LPS-treated CD-1 mice[3].
References:
[1] ua X, Church K, Walker W, et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Positive Modulator of HGF/MET, Fosgonimeton, in Healthy Volunteers and Subjects with Alzheimer's Disease: Randomized, Placebo-Controlled, Double-Blind, Phase I Clinical Trial. J Alzheimers Dis. 2022;86(3):1399-1413.
[2] Reda SM, Setti SE, Berthiaume AA, et al. Fosgonimeton attenuates amyloid-beta toxicity in preclinical models of Alzheimer's disease. Neurotherapeutics. 2024;21(4):e00350.
[3] Johnston JL, et al. Fosgonimeton, a Novel Positive Modulator of the HGF/MET System, Promotes Neurotrophic and Procognitive Effects in Models of Dementia. Neurotherapeutics. 2023 Mar;20(2):431-451.
Fosgonimeton是一种高度特异性的HGF/MET（肝细胞生长因子/间充质-上皮转化因子受体）神经营养系统的小分子正向调节剂。Fosgonimeton是一种适合皮下给药的前药，可在血浆中迅速转化为活性代谢物fosgo-AM。Fosgo-AM能够穿过血脑屏障，增强肝细胞生长因子（HGF）与其络氨酸激酶受体（MET）的相互作用，通过PI3k/Akt和MAPK通路诱导下游信号传导，并通过蛋白激酶C增强N-methyl-D-aspartate（NMDA）受体介导的长期增强作用，在痴呆症的临床前模型中已显示出神经营养和促进认知的效果[1][2]。
体内实验中，在Aβ肽处理的成年雄性Wistar大鼠中，皮下注射Fosgonimeton（0.125、0.25、0.5、1 和 2mg/kg）连续14天，在所有测试剂量下均显著恢复了大鼠认知功能[2]。连续14天以0.25、0.5和1.25mg/kg剂量对LPS处理的CD-1小鼠进行Fosgonimeton皮下给药，均显著改善了小鼠认知功能缺陷[3]。
| Animal experiment [1]: | |
Animal models | Aβ peptides treated adult male Wistar rats |
Preparation Method | Fosgonimeton (0.125, 0.25, 0.5, 1, or 2mg/kg) or vehicle were administered subcutaneously from day of surgery (study day 0) to study day 14. On study day 14, rats underwent the passive avoidance acquisition paradigm, where entering a darkened compartment is associated with receiving a mild foot shock. |
Dosage form | 0.125, 0.25, 0.5, 1 and 2mg/kg/d; 14d; s.c. |
Applications | Significantly restored cognitive function at all doses tested. The maximum average degree of recovery was 88% recovery in 0.125mg/kg treated group. |
References: | |
| Cas No. | 2093305-05-4 | SDF | Download SDF |
| 别名 | 肝细胞生长因子受体激动剂多肽,ATH-1017 | ||
| 分子式 | C27H45N4O8P | 分子量 | 584.64 |
| 溶解度 | DMSO : 125 mg/mL (213.81 mM; Need ultrasonic) | 储存条件 | Store at -20°C, protect from light, stored under nitrogen |
| 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 | 1.7105 mL | 8.5523 mL | 17.1045 mL |
| 5 mM | 342.1 μL | 1.7105 mL | 3.4209 mL |
| 10 mM | 171 μL | 855.2 μL | 1.7105 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。
Quality Control & SDS
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- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet