Letermovir
(Synonyms: 莱莫维韦; AIC246) 目录号 : GC12672
A selective inhibitor of HCMV replication
Cas No.:917389-32-3
Sample solution is provided at 25 µL, 10mM.
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AIC246, also known as letermovir, is a novel anti-CMV compound with IC50 value of 5.1 ± 1.2 nM. It targets the pUL56 (amino acid 230-370) subunit of the viral terminase complex [1].
The subunit pUL56 is a component of the terminase complex which is responsible for packaging unit length DNA into assembling virions.
AIC246 has a novel mode of action targets the enzyme UL56 terminase and keep active to other drug-resistant virus. The anti-HCMV activity of AIC246 was evaluated in vitro by using different HCMV laboratory strains, GCV-resistant viruses. The result showed that the inhibitory potentcy of AIC246 surpasses the current gold standard GCV by more than 400-fold with respect to EC50s (mean, ∼4.5 nM versus ∼2 μM) and by more than 2,000-fold with respect to EC90 values (mean, ∼6.1 nM versus ∼14.5 μM). In the CPE-RA strains, the EC50 values of AIC 246 ranged from 1.8 nM to 6.1 nM [2].
In mouse model with HCMV subcutaneous xenograft, oral administration of AIC246 caused significant a dose-dependent reduction of the HCMV titer. 30 mg/kg/d AIC246 for 9 days induced PFU reduction with maximum efficiency, compared with the gold standard GCV at the ED50 and ED90 level [2].
References:
[1].Verghese PS, Schleiss MR. Letermovir Treatment of Human Cytomegalovirus Infection Anti-infective Agent. Drugs Future. 2013, 38(5):291-298.
[2]. Lischka P1, Hewlett G, Wunberg T, et al.In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246.Antimicrob Agents Chemother. 2010, 54(3):1290-1297.
Cell experiment: | Briefly, 5×103 AD169-infected NHDF cells/well are seeded into the wells of 30 96-well microtiter plates. The infection is allowed to proceed under the exposure of 50 nM AIC246 (10×EC50) until a CPE developed in one or more of the compound-treated wells (indicative of resistant virus breakthrough). Noninfected and nontreated cells serve as controls on each plate. Mutant virus amplification is accomplwashed after cultures achieved maximum CPE by the passage of cell-free supernatant virus in the presence of 50 nM AIC246. The resultant AIC246-resistant progeny virus mutants are plaque purified three times by limiting dilutions in the presence of AIC246. The stability of resistance is tested by serially passaging plaque-purified viruses without selective pressure (8 to 10 times). |
Animal experiment: | Mice (18 to 25 g body weight) are anesthetized, and the Gelfoam sponges are implanted subcutaneously in the dorsoscapular area. After transplantation, mice are randomized and grouped in 10 animals per treatment group. Starting 4 h after transplantation, mice are treated once daily with letermovir for nine consecutive days. Drugs are applied per os by oral gavage. Total administration volume is 10 mL/kg. Mice are sacrificed after 9 days of treatment, and the Gelfoam implants are removed and digested with collagenase at 37°C. After 2 to 3 h, human cells are recovered by centrifugation and resuspended in GM. Subsequently, the isolated cell suspensions are serially diluted and mixed with uninfected NHDF indicator cells and PFU are determined by plaque assays as described above. Virus titers determined from isolated cells are given as PFU/mL. |
References: [1]. Marschall M, et al. In vitro evaluation of the activities of the novel anticytomegalovirus compound AIC246 (letermovir) against herpesviruses and other human pathogenic viruses. Antimicrob Agents Chemother. 2012 Feb;56(2):1135-7. | |
| Cas No. | 917389-32-3 | SDF | |
| 别名 | 莱莫维韦; AIC246 | ||
| 化学名 | 2-[(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4H-quinazolin-4-yl]acetic acid | ||
| Canonical SMILES | COC1=C(C=C(C=C1)C(F)(F)F)N2C(C3=C(C(=CC=C3)F)N=C2N4CCN(CC4)C5=CC(=CC=C5)OC)CC(=O)O | ||
| 分子式 | C29H28F4N4O4 | 分子量 | 572.55 |
| 溶解度 | ≥ 57.3 mg/mL in DMSO | 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 | 1.7466 mL | 8.7329 mL | 17.4657 mL |
| 5 mM | 0.3493 mL | 1.7466 mL | 3.4931 mL |
| 10 mM | 0.1747 mL | 0.8733 mL | 1.7466 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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet