LY450108
(Synonyms: N-[4-[(1R)-1-甲基-2-[[异丙基磺酰基]氨基]乙基]苯基]-3,5-二氟苯基甲酰胺) 目录号 : GC36515
LY450108是AMPA受体增强剂。
Cas No.:376594-67-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
LY450108 is an alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor potentiator. IC50 value: Target: AMPA receptors mediate most of the excitatory neurotransmission and play a key role in synaptic plasticity in the mammalian central nervous system (CNS). Recent evidence has shown that in addition to modulating fast synaptic plasticity and memory processes, AMPA receptor potentiators alter downstream signalling pathways and may thereby have utility in other CNS disorders.
[1]. Simon E Ward1, Benjamin D Bax, Mark Harries. Challenges for and current status of research into positive modulators of AMPA receptors. British Journal of Pharmacology. 2010,160(2):181-190. [2]. O'Neill MJ, Witkin JM. AMPA receptor potentiators: application for depression and Parkinson's disease. Curr Drug Targets. 2007 May;8(5):603-20. [3]. Jhee SS, Chappell AS, Zarotsky V, et al. Multiple-dose plasma pharmacokinetic and safety study of LY450108 and LY451395 (AMPA receptor potentiators) and their concentration in cerebrospinal fluid in healthy human subjects. J Clin Pharmacol. 2006 Apr;46(4):424-32. [4]. Douglas A. Schober, Martin B. Gill, Hong Yu, et al. Transmembrane AMPA Receptor Regulatory Proteins and Cornichon-2 Allosterically Regulate AMPA Receptor Antagonists and Potentiators. The Journal of Biological Chemistry, 286, 13134-13142.
| Cas No. | 376594-67-1 | SDF | |
| 别名 | N-[4-[(1R)-1-甲基-2-[[异丙基磺酰基]氨基]乙基]苯基]-3,5-二氟苯基甲酰胺 | ||
| Canonical SMILES | FC1=CC(F)=CC(C(NC2=CC=C([C@@H](C)CNS(C(C)C)(=O)=O)C=C2)=O)=C1 | ||
| 分子式 | C19H22F2N2O3S | 分子量 | 396.45 |
| 溶解度 | DMSO: ≥ 50 mg/mL (126.12 mM); Water: < 0.1 mg/mL (insoluble) | 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 | 2.5224 mL | 12.6119 mL | 25.2239 mL |
| 5 mM | 0.5045 mL | 2.5224 mL | 5.0448 mL |
| 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 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。
Preventive effects of the AMPA receptor potentiator LY450108 in an LPS-induced depressive mouse model
Behav Brain Res 2022 Apr 29;424:113813.PMID:35202718DOI:10.1016/j.bbr.2022.113813.
Previous studies have demonstrated a close association between α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) and depressive disorders, and activation of AMPARs may represent a promising way to treat depression. However, the effects of AMPAR potentiators on depression and the underlying mechanism have not been comprehensively clarified. We used lipopolysaccharide (LPS) to establish a depressive mouse model and an in vitro damage model of SH-SY5Y cells, and the AMPAR potentiator LY450108 was introduced to the study. We found that LY450108 alleviated LPS-induced depressive behavior and abnormal phosphorylation of hippocampal AMPARs in mice. LY450108 also alleviated LPS-induced apoptosis and decreased the viability of SH-SY5Y cells. In addition, LY450108 protected SH-SY5Y cells from LPS-induced abnormal phosphorylation of AMPARs. In conclusion, our findings suggest that LY450108 has antidepressant effects against LPS-induced neuronal damage and depression.
Multiple-dose plasma pharmacokinetic and safety study of LY450108 and LY451395 (AMPA receptor potentiators) and their concentration in cerebrospinal fluid in healthy human subjects
J Clin Pharmacol 2006 Apr;46(4):424-32.PMID:16554450DOI:10.1177/0091270006286899.
The objective of this study was to measure the steady-state cerebrospinal fluid (CSF) concentration of LY450108 and LY451395 (positive modulators of AMPA receptors) in healthy subjects after the administration of 1 mg and 5 mg. Secondary objectives included the evaluation of safety, pharmacokinetics, and steady-state ratio of plasma:CSF concentrations of LY450108 and LY451395 after multiple dosing. This study was an open-label, multiple oral dose study evaluating 1 mg and 5 mg LY450108 and 1 mg and 5 mg LY451395 in 12 (3 subjects per dosing group) healthy subjects, aged 18 to 49 years. Twelve healthy male subjects completed the study. LY450108 and LY451395 were quantifiable in CSF after 1-mg and 5-mg multiple-dose administrations with plasma:CSF ratio of 82:1 and 44:1, respectively. LY450108 and LY451395 1 mg and 5 mg were measured in the CSF. Single and multiple oral doses of LY450108 and LY451395 were determined to be safe and well tolerated in healthy subjects.
AMPA receptor potentiators: application for depression and Parkinson's disease
Curr Drug Targets 2007 May;8(5):603-20.PMID:17504104DOI:10.2174/138945007780618517.
Alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors mediate most of the excitatory neurotransmission and play a key role in synaptic plasticity in the mammalian central nervous system (CNS). In recent years several classes of AMPA receptor potentiators have been reported in the literature, including pyrrolidones (piracetam, aniracetam), benzothiazides (cyclothiazide), benzylpiperidines (CX-516, CX-546) and biarylpropylsulfonamides (LY392098, LY404187, LY450108, LY451395 and LY503430). Clinical and preclinical data have suggested that positive modulation of AMPA receptors may be therapeutically effective in the treatment of cognitive deficits. However, recent evidence has shown that in addition to modulating fast synaptic plasticity and memory processes, AMPA receptor potentiators alter downstream signalling pathways and may thereby have utility in other CNS disorders. The present review summarises studies into the effects of AMPA receptor potentiators (with a focus on the biarylpropylsulfonamides) in rodent models of depression and Parkinson's disease.