Letermovir是一种口服抗病毒化合物，可抑制巨细胞病毒（CMV）DNA terminase，EC50值为4.0nM。
Cas No.:917389-32-3
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Letermovir is an orally antiviral compound that inhibits the cytomegalovirus (CMV) DNA terminase, with an EC50 value of 4.0nM [1]. Letermovir inhibits the viral terminase complex at pUL56 and pUL51 resulting in the cleavage of viral genomic units and accumulation of immature viral DNA, thereby inhibiting CMV replication [2]. The effect of Letermovir is in the prevention of the cleavage of long DNA concatemers into individual viral subunits, thereby resulting in noninfectious long DNA particles [3]. Letermovir has been widely used to reduce the incidence of CMV infection during allogeneic hematopoietic stem cell transplantation[4].
In vitro, Letermovir treatment for 6 days at 24nM reduced the CMV (BADrUL131-Y) replication in ARPE-19 cells[5].
In vivo, Letermovir treatment via oral administration at a dose of 30mg/kg/day for 9 days led to a notable reduction of the CMV titer within transplanted NHDF cells infected with CMV in the mouse xenograft model [6].
References:
[1] Wildum S, Zimmermann H, Lischka P. In vitro drug combination studies of Letermovir (AIC246, MK-8228) with approved anti-human cytomegalovirus (HCMV) and anti-HIV compounds in inhibition of HCMV and HIV replication[J]. Antimicrobial agents and chemotherapy, 2015, 59(6): 3140-3148..
[2] Marty F M, Ljungman P, Chemaly R F, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation[J]. New England Journal of Medicine, 2017, 377(25): 2433-2444.
[3] El Helou G, Razonable R R. Letermovir for the prevention of cytomegalovirus infection and disease in transplant recipients: an evidence-based review[J]. Infection and drug resistance, 2019: 1481-1491.
[4] Chemaly R F, Ullmann A J, Stoelben S, et al. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation[J]. New England Journal of Medicine, 2014, 370(19): 1781-1789.
[5] Giménez E, Guerreiro M, Gozalbo-Rovira R, et al. In vitro assessment of the combined effect of letermovir and sirolimus on cytomegalovirus replication[J]. Revista Española de Quimioterapia, 2023, 36(5): 526.
[6] Lischka P, Hewlett G, Wunberg T, et al. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246[J]. Antimicrobial agents and chemotherapy, 2010, 54(3): 1290-1297.
Letermovir是一种口服抗病毒化合物，可抑制巨细胞病毒（CMV）DNA terminase，EC50值为4.0nM[1]。Letermovir抑制pUL56和pUL51位点的病毒终止酶复合物，导致病毒基因组单位切割受阻及未成熟病毒DNA积累，从而抑制CMV复制[2]。Letermovir的作用是阻止长DNA连环体切割成单个病毒亚单位，从而产生无感染性的长DNA颗粒[3]。Letermovir已被广泛用于降低异基因造血干细胞移植期间CMV感染的发生率[4]。
在体外，使用24nM的Letermovir处理6天，可减少ARPE-19细胞中CMV（BADrUL131-Y）的复制 [5]。
在体内，在移植了感染了CMV的NHDF细胞的小鼠异种移植模型中，每日口服30mg/kg剂量的Letermovir，持续9天，显著降低了CMV滴度[6]。
| Cell experiment [1]: | |
Cell lines | ARPE-19 cells |
Preparation Method | ARPE-19 cells were seeded in white 96-well plates containing DMEM/F12 medium supplemented with 10% fetal calf serum, 10000IU/ml penicillin and 10mg/ml streptomycin. ARPE-19 cells were seeded in 96-well microtiter plates (4×104 cells/well) for 24h at 37ºC and 5% CO2 and infected with 0.1MOI of CMV strain BADrUL131-Y for 2h in DMEM/F-12K medium containing Letermovir (0.38, 0.75, 1.5, 3, 6, 12, and 24nM). The plates were incubated for 6 days, and the antiviral activity was determined. |
Reaction Conditions | 0.38, 0.75, 1.5, 3, 6, 12, and 24nM; 6 days |
Applications | Letermovir treatment reduced the CMV replication in ARPE-19 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | NOD SCID mice |
Preparation Method | NOD SCID mice were housed under sterile conditions in individually ventilated cages with filter top lids. All mice were adaptively fed for one week. Gelfoam hemostyptic gelatin devices were cut aseptically into 1-cm2 pieces. These implants were soaked in NHDF cell culture growth medium (GM), and sponges were brought to 37°C in a CO2 incubator. NHDF cells were infected with cell-free CMV strain at an MOI of 0.03. After 4h, cells were collected by trypsinization followed by centrifugation at room temperature for 10min at 800×g. Cells were resuspended in GM and counted using a hemocytometer. Each Gelfoam implant was seeded with a suspension of 1×106 infected cells by pipetting the cells onto the sponges. Human cells were allowed to adhere to the collagen sponges for at least 3 to 4h at 37°C. To enhance vascularization of the implant, 250ng recombinant human basic fibroblast growth factor was pipetted onto each implant 1h prior to transplantation. Mice (18 to 25g) were anesthetized, and the Gelfoam sponges were implanted subcutaneously in the dorsoscapular area. After transplantation, mice were randomized and grouped in 10 animals per treatment group. Starting 4h after transplantation, mice were treated once daily with the Letermovir for nine consecutive days by oral gavage at a dose of 30mg/kg. After a 9-day treatment period, Gelfoam sponges were explanted and the number of CMV PFU was determined. |
Dosage form | 30mg/kg/day for 9 days; p.o. |
Applications | Letermovir treatment led to a notable reduction of the CMV titer within transplanted cells in the mouse xenograft model. |
References: | |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.7466 mL | 8.7329 mL | 17.4657 mL |
| 5 mM | 349.3 μL | 1.7466 mL | 3.4931 mL |
| 10 mM | 174.7 μL | 873.3 μL | 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: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet