AVN-492
目录号 : GC30907
A 5-HT6 receptor antagonist
Cas No.:1220646-23-0
Sample solution is provided at 25 µL, 10mM.
AVN-492 is an antagonist of the serotonin (5-HT) receptor subtype 5-HT6 (Ki = 0.09 nM).1 It selectively inhibits the 5-HT6 receptor over the 5-HT2B receptor (IC50s = 0.19 and 268 nM, respectively, in a radioligand binding assay). AVN-492 inhibits increases in cAMP levels induced by 5-HT in HEK293 cells expressing the 5-HT6 receptor (IC50 = 1.5 nM). It increases the time spent in the open arms of the elevated plus maze in rats, indicating anxiolytic activity, when administered at a dose of 0.2 mg/kg. AVN-492 (1 mg/kg) also prevents memory deficits induced by the NMDA receptor antagonist MK-801 in a passive avoidance test.
1.Ivachtchenko, A.V., Okun, I., Aladinskiy, V., et al.AVN-492, a novel highly selective 5-HT6R antagonist: Preclinical evaluationJ. Alzheimers Dis.58(4)1043-1063(2017)
Kinase experiment: |
AVN-492 is dissolved into 100% DMSO to a concentration of 10mM. This DMSO solution is then diluted 50-fold with either anMQ water or a buffer with corresponding pH[1].The Caco-2 permeability assay is performed using the MultiScreen 96-well plates. In short, the Caco-2 cells (ATCC, Cat. No HTB-37) are seeded into each well with a porous membrane bottom. The cells are grown for 20-23 days at 37°C in CO2 thermostat until total confluence. The growth medium is changed every 2-3 days. The physical integrity of the cell monolayer established on the well porous membrane is tested using a “leak test” with Lucifer Yellow CH. Permeability ofAVN-492 (200μM) is determined in both directions, the apical-to-basal and basal-to-apical. Permeabilities of comparison compounds Ranitidine (lowpermeability) and Propranolol (high permeability) are measured in apical-to-basal direction only. The Pgp-dependent permeability of Rhodamine 123 (30 μM) is determined with or without the Pgp inhibitor Verapamil (100 μM). To assess participation of the Pgp pump in a possible efflux of AVN-492, the apical-to-basal and basalto-apical permeabilities are also registered in the presence of Verapamil. Concentrations of AVN-322 in donor and acceptor chambers are determined using LC/MS/MS API2000. The apparent permeability is calculated[1]. |
Animal experiment: |
Mice and Rats[1] For pharmacokinetic, behavior, and toxicity studies, male Wistar rats (220-242 g), male CD1 mice (24-30 g), male SHK mice (20-25 g), and male Balb/C mice (15-20 g) are used. The pharmacokinetic profiling of AVN-492 is performed on male CD-1 mice and male Wistar rats. Each dose-route group of rodents consist of 3 animals. AVN-492 is administered either intravenously (IV) or orally (PO). At different time points after the drug administration, the animals are quickly euthanized by placing them into CO2 chamber. Blood samples are drawn through a cardiopuncture. In separate experiments, AVN-492 is orally administered to male Wistar rats at doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg (3 independent groups, 3 animals per group). The animals are anesthetized 60 min later with 5% halothane, positioned in a stereotaxic frame, and samples of cerebrospinal fluid (CSF) are taken through 23G needle from the cisterna magna. CSF samples are checked for the absence of blood contamination. After the CSF samples are taken, the blood samples are drawn through a cardiopuncture and the brains are removed, washed immediately with ice-cold saline, and homogenized in a 1:4 brain tissue/water mixture. AVN-492 is extracted from all the samples with acetonitrile and concentrations are determined using LC/MS/MS API2000. |
References: [1]. Ivachtchenko AV, et al. AVN-492, A Novel Highly Selective 5-HT6R Antagonist: Preclinical Evaluation. J Alzheimers Dis. 2017;58(4):1043-1063. |
Cas No. | 1220646-23-0 | SDF | |
Canonical SMILES | O=S(C1=CC=CC=C1)(C2=C3N(C(C)=C(N(C)C)C(C)=N3)N=C2NC)=O | ||
分子式 | C17H21N5O2S | 分子量 | 359.45 |
溶解度 | DMSO : ≥ 100 mg/mL (278.20 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 | 2.782 mL | 13.9101 mL | 27.8203 mL |
5 mM | 0.5564 mL | 2.782 mL | 5.5641 mL |
10 mM | 0.2782 mL | 1.391 mL | 2.782 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
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet