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| 25mg |
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Purity: ≥98%
Maribavir (1263W94; BW-1263W94; GW-1263; SHP-620; GW-257406X; VP-41263; Livtencity), an experimental oral antiviral (anti-CMV) drug candidate, is a novel and potent inhibitor of histone phosphorylation catalyzed by wild-type pUL97 in vitro with an IC50 of 3 nM. As of December 2021, Maribavir has been approved as the first drug for treating adults and pediatric patients with post-transplant cytomegalovirus (CMV) infection/disease that does not respond to available antiviral treatment for CMV. Livtencity works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication. Maribavir has potent antiviral activity against HCMV and Epstein-Barr virus (EBV). Maribavir is licensed by ViroPharma from GlaxoSmithKline in 2003 for the prevention and treatment of human cytomegalovirus (HCMV) disease in hematopoietic stem cell/bone marrow transplant patients.
| Targets |
HCMV
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|---|---|
| ln Vitro |
Maribavir, with a mean IC50 of 35 nM, is a strong inhibitor of autophosporylation of both the wild type and all of the major Ganciclovir (GCV) resistant UL97 mutants that have been studied. With an IC50 of 4.8 nM, the M460I mutation causes hypersensitivity to maribavir. L397R, a UL97 mutant resistant to maribavir, exhibits reduced function as a Ganciclovir kinase and protein kinase (~10% of wild type levels). Maribavir is a competitive inhibitor of ATP with a Ki of 10 nM, as shown by enzyme kinetic studies[1]. Using a multicycle DNA hybridization assay, maribavir (1263W94) inhibits viral replication in a dose-dependent manner with an IC50 of 0.12±0.01 μM. Maribavir significantly inhibits the pUL97 protein kinase, with 50% inhibition happening at 3 nM[2].
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| Enzyme Assay |
Using increasing concentrations of ATP (2 μM to 20 μM), enzyme kinetic analysis is carried out on the purified wild type and mutant UL97 protein species. To calculate the Km for ATP for each UL97 species, the amount of incorporated radiolabelled phosphate is plotted against the concentration of ATP in a Lineweaver Burke plot. Protein kinase assays are used to measure the impact of Maribavir on the rate of radiolabelled phosphate incorporation by either wild type or mutant UL97.The assays can be conducted at a fixed concentration of 0.55 μM of Maribavir, as previously mentioned, or with increasing concentrations of 0.01 μM to 5.0 μM of Maribavir to determine the IC50 of Maribavir for each species of UL97.Plots of 1/v vs 1/ATP with increasing Maribavir concentrations are created to ascertain the type of inhibition mediated by Maribavir. If the family of lines converged at 1/Vmax on the y-axis, then there was clear evidence of competitive inhibition. The Ki is computed using the variation in slope brought about by the addition of Maribavir[1].
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| Cell Assay |
MRC-5 cells are cultivated for three days in MEM 8-1-1 until confluence (~1.1×105 cells/well), after being seeded in 24-well plates at a density of approximately 5×104 cells/well. In MEM 2-1-1, the cells are infected with AD169 at a multiplicity of infection (MOI) of 1 to 3, and the infection is allowed to adsorb for 90 minutes at 37°C. One milliliter of MEM 2-1-1 is added in place of the unadsorbed virus. Maribavir, BDCRB, or GCV are added to the medium at the concentrations specified for each experiment to examine the impact of the compounds on viral DNA synthesis or maturation[2].
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| References |
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| Molecular Formula |
C15H19CL2N3O4
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|---|---|
| Molecular Weight |
376.23506
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| Exact Mass |
375.08
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| Elemental Analysis |
C, 47.89; H, 5.09; Cl, 18.84; N, 11.17; O, 17.01
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| CAS # |
176161-24-3
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| Appearance |
Solid powder
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| SMILES |
ClC1=C(Cl)C=C2C(N=C(NC(C)C)N2[C@@H]3[C@@H](O)[C@@H](O)[C@H](CO)O3)=C1
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| InChi Key |
KJFBVJALEQWJBS-XUXIUFHCSA-N
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| InChi Code |
InChI=1S/C15H19Cl2N3O4/c1-6(2)18-15-19-9-3-7(16)8(17)4-10(9)20(15)14-13(23)12(22)11(5-21)24-14/h3-4,6,11-14,21-23H,5H2,1-2H3,(H,18,19)/t11-,12-,13-,14-/m0/s1
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| Chemical Name |
5,6-Dichloro-2-(isopropylamino)-1-beta-L-ribofuranosyl-1H-benzimidazole
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| Synonyms |
1263-W94; GW-1263; SHP-620; 1263 W94; 1263W-94; BW1263W 94; GW1263; SHP620; BW-1263W94; VP41263; Livtencity; BW 1263W94; VP-41263; GW-257406X; GW257406-X; GW 257406X; GW 257406 X; GW257406X
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~200 mg/mL (~531.58 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.87 mg/mL (7.63 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.87 mg/mL (7.63 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.64 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (6.64 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (6.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 6: 5% DMSO+40% PEG300+5% Tween-80+50% Saline: ≥ 2.87 mg/mL (7.63 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6579 mL | 13.2894 mL | 26.5788 mL | |
| 5 mM | 0.5316 mL | 2.6579 mL | 5.3158 mL | |
| 10 mM | 0.2658 mL | 1.3289 mL | 2.6579 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Effects of maribavir on the autophosphorylation of wild type UL97 and the various mutant proteins.Herpesviridae. 2010; 1: 4. |
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 IC50of maribavir for the wild type and mutant UL97 Proteins.Herpesviridae. 2010; 1: 4. |
 Competitive inhibition of ATP binding by maribavir. Protein kinase assays were performed containing increasing concentrations of ATP (2 μM-20 μM) in the absence of maribavir (0.0 μM on the graph) and repeated for increasing maribavir concentrations (0.01 μM, 0.015 μM, 0.2 μM or 0.25 μM).Herpesviridae. 2010; 1: 4. |
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