Letermovir

SKU: orb1301825

Description

Letermovir

Research Area

Infectious Disease & Virology, Protein Biochemistry

Key Properties

• CAS Number: 917389-32-3
• MW: 572.55
• Purity: 99.85%
• Formula: C₂₉H₂₈F₄N₄O₄
• SMILES: COc1cccc(c1)N1CCN(CC1)C1=Nc2c(F)cccc2[C@H](CC(O)=O)N1c1cc(ccc1OC)C(F)(F)F
• Target: Virus Protease,HCV Protease
• Solubility: Ethanol:2 mg/mL (3.49 mM);DMSO:70 mg/mL (122.26 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.49 mM)

Bioactivity

• Target IC50:
  HCMV:~5 nM (in fibroblast cells)
• In Vivo:
  Letermovir treatment led to a dose-dependent reduction o the H mV titer in transplanted cells compared to that o the placebo-treated control group usin the mouse xenograft model. Statistical analysis revealed significant antiviral effects fo the 10-, 30-, and 100 mg/kg/day treatment groups of Letermovir as well as fo 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 12 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.
• In Vitro:
  The inhibitory potency of Letermovir surpasses ganciclovir (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). NHDF monolayers showed no microscopically apparent cytotoxic effects at Letermovir concentration of < 3 μM when observed during antiviral assays. Letermovir is remarkably specific for human cytomegaloviruses since no significant activity was noted against any Other herpesvirus tested the EC50s obtained for R mV and MCMC indicated that no (RCMV) or only a very low-level (MCMV, 4.51 μM) Letermovir sensitivity could be detected even for rodent cytomegaloviruses.
• Cell Research:
  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% throughou the whole plate). After a 7-day incubation period, alamarBlue solution was added to each well an 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 agains the logarithm of drug concentration . Drug concentration 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 calculat the selectivity index (SI = CC50/EC50) for individual substances.
• Animal Research:
  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 H mV 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 pipettin the cells ont the sponges. Human cells were allowed to adhere to the collagen sponges for at least 3 to 4 h at 37℃. To enhance vascularization o 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, an the Gelfoam sponges were implanted Subcutaneously in the dorsoscapular area. After transplantation, mice were andomized and grouped in ～10 animals per treatment group. Starting 4 h after transplantation, mice were treated once daily wit the indicated compounds for nine consecutive days. Drugs were applied per os by oral gavage. Total administration volume was 10 L/kg. Mice were sacrificed after 9 days of treatment, an the Gelfoam implants were removed and digested with collagenase at 37℃. After 2 to 3 h, human cells were recovered by centrifugation and resuspended in GM. Subsequently the isolated cell suspensions were serially diluted and mixed with uninfected NHDF indicator cells and PFU were determined by plaque assays. Virus titers determined from isolated cells are given as PFU/ml.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

Inhibitor, HCMV, HCV Protease, HCVProtease, Letermovir, MK8828, MK-8828, MK 8828, inhibit, AIC 246, AIC246, AIC-246, CMV, Cytomegalovirus

Compound Identifiers

PubChem CID

45138674