Letermovir (Synonyms: AIC246) |
Catalog No.GC12672
One-Click Copy Product Info
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Letermovir is an orally antiviral compound that inhibits the cytomegalovirus (CMV) DNA terminase, with an EC50 value of 4.0nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 917389-32-3
Sample solution is provided at 25 µL, 10mM.
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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.
| 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 | |
| Synonyms | AIC246 | ||
| Chemical Name | 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 | ||
| Formula | C29H28F4N4O4 | M.Wt | 572.55 |
| Solubility | ≥ 57.3 mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)