| 产品描述： | Letermovir (AIC246) is a novel anti-CMV compound (EC50: about 5 nM in fibroblast cells). It targets the pUL56 subunit of the viral terminase complex. |
| 靶点： |
HCV Protease;HCVProtease |
| 体内研究： |
AIC246 treatment led to a dose-dependent reduction of the HCMV titer in transplanted cells compared to that of the placebo-treated control group using the mouse xenograft model. Statistical analysis revealed significant antiviral effects for the 10-, 30-, and 100-mg/kg/day treatment groups of AIC246 as well as for the 100-mg/kg/day VGCV control group. The incidence of prophylaxis failure with letermovir, as compared with placebo, was 48% versus 64% at a daily letermovir dose of 60 mg, 32% at a dose of 120 mg, and 29% at a dose of 240 mg. Kaplan-Meier time-to-onset profiles for prophylaxis failure showed a significant difference in the comparison of letermovir at a dose of 240 mg per day with placebo |
| 细胞实验： |
Briefly, 96-well microtiter plates were seeded with 1.5 × 10^4 cells/well and incubated overnight. Drugs were added to the wells in 3-fold serial dilutions starting from 0.33 mM (the DMSO concentration was kept constant at 0.66% throughout the whole plate). After a 7-day incubation period, alamarBlue solution was added to each well and the fluorescence signal was measured using a SpectraFluor Plus fluorescence reader. The relative fluorescence units of treated wells were expressed as percentages of untreated cell control wells and plotted against the logarithm of drug concentrations. Drug concentrations reducing cell viability by 50% (CC50s) were determined from dose-response curves. The assays were performed at least three times with duplicate samples. CC50 values were used to calculate the selectivity index (SI = CC50/EC50) for individual substances |
| 动物实验： |
Briefly, 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 HCMV strain Davis at an MOI of 0.03. After 4 h, cells were collected by trypsinization followed by centrifugation at room temperature for 10 min at 800 × g. Cells were resuspended in GM and counted using a hemocytometer. Each Gelfoam implant was seeded with a suspension of 1 × 10^6 infected cells by pipetting the cells onto the sponges. Human cells were allowed to adhere to the collagen sponges for at least 3 to 4 h at 37°C. To enhance vascularization of the implant, 250 ng recombinant human basic fibroblast growth factor was pipetted onto each implant 1 h prior to transplantation. Mice (18 to 25 g body weight) were anesthetized, and the Gelfoam sponges were implanted subcutaneously in the dorsoscapular area. After transplantation, mice were randomized and grouped in |
| 参考文献： |
1. Chemaly RF, et al. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation.N Engl J Med. 2014 May 8;370(19):1781-9. 2. Lischka P, et al. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother. 2010 Mar;54(3):1290-7. 3. 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. |
| 溶解性： |
Soluble in DMSO、Ethanol |
| 保存条件： |
-20℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.747 ml |
8.733 ml |
17.466 ml |
| 5 mM |
0.349 ml |
1.747 ml |
3.493 ml |
| 10 mM |
0.175 ml |
0.873 ml |
1.747 ml |
| 50 mM |
0.035 ml |
0.175 ml |
0.349 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京