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Maribavir

Catalog No. T2162   CAS 176161-24-3
Synonyms: BW1263W94, GW257406X, Benzimidavir, 1263W94

Maribavir (GW257406X) is an orally available benzimidazole riboside compound with activity against cytomegalovirus (CMV). Maribavir is a selective ATP competitor of the viral UL97 kinase, which is involved in viral nuclear maturation events, such as viral DNA assembly and movement of viral capsids from the nucleus of infected cells. Maribavir has activity against strains of CMV that are resistant to standard anti-CMV agents.

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Maribavir Chemical Structure
Maribavir, CAS 176161-24-3
Pack Size Availability Price/USD Quantity
1 mg In stock $ 36.00
2 mg In stock $ 51.00
5 mg In stock $ 89.00
10 mg In stock $ 143.00
25 mg In stock $ 259.00
50 mg In stock $ 433.00
100 mg In stock $ 643.00
1 mL * 10 mM (in DMSO) In stock $ 97.00
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Purity: 100%
Purity: 100%
Purity: 99.85%
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Biological Description
Chemical Properties
Storage & Solubility Information
Description Maribavir (GW257406X) is an orally available benzimidazole riboside compound with activity against cytomegalovirus (CMV). Maribavir is a selective ATP competitor of the viral UL97 kinase, which is involved in viral nuclear maturation events, such as viral DNA assembly and movement of viral capsids from the nucleus of infected cells. Maribavir has activity against strains of CMV that are resistant to standard anti-CMV agents.
Targets&IC50 Histone phosphorylation:3 nM
In vitro Maribavir effectively inhibits the autophosphorylation of both the wild type and the major Ganciclovir (GCV)-resistant UL97 mutants, showing a mean IC50 of 35 nM. The M460I mutation increases sensitivity to Maribavir, decreasing its IC50 to 4.8 nM. However, a Maribavir-resistant UL97 mutant (L397R) exhibits significantly reduced kinase activity, functioning at approximately 10% of the wild type levels for both GCV kinase and protein kinase activities. Enzyme kinetic studies reveal that Maribavir acts as a competitive inhibitor against ATP, with a Ki of 10 nM. Furthermore, Maribavir inhibits viral replication in a dose-dependent manner, achieving an IC50 of 0.12±0.01 μM as per a multicycle DNA hybridization assay, and strongly inhibits pUL97 protein kinase with a 50% inhibition concentration of 3 nM.
Kinase Assay Enzyme kinetic analysis is performed on the purified wild type and mutant UL97 protein species using increasing concentrations of ATP (2 μM to 20 μM). The amount of incorporated radiolabelled phosphate is plotted against the concentration of ATP in a Lineweaver Burke plot to determine the Km for ATP for each UL97 species. The effect of Maribavir upon the rate of radiolabelled phosphate incorporation by wild type or mutant UL97 is determined by protein kinase assays at a fixed concentration of Maribavir (0.5 μM) as above, or with increasing concentrations of Maribavir (0.01 μM to 5.0 μM) to determine the IC50 of Maribavir for each UL97 species. In order to determine the nature of the inhibition mediated by Maribavir, plots of 1/v vs 1/ATP with increasing concentrations of Maribavir are constructed. Competitive inhibition is evident if the family of lines cconverged on the y-axis at 1/Vmax. The change in slope caused by the addition of Maribavir is used to calculate the Ki[1].
Cell Research Maribavir (1263W94) is dissolved in DMSO and stored, and then diluted with appropriate media before use[2]. For these studies MRC-5 cells are seeded in 24-well plates at ~5×104 cells/well and grown for 3 days in MEM 8-1-1 to confluence (~1.1×105 cells/well). The cells are infected with AD169 in MEM 2-1-1 at an MOI ranging from 1 to 3 and incubated at 37°C for 90 min to allow viral adsorption. The unadsorbed virus is removed and replaced with 1 mL of MEM 2-1-1. To test the effect of compounds on viral DNA synthesis or maturation, Maribavir, BDCRB, or GCV is added to the medium at the concentrations indicated for each experiment[2].
Synonyms BW1263W94, GW257406X, Benzimidavir, 1263W94
Molecular Weight 376.24
Formula C15H19Cl2N3O4
CAS No. 176161-24-3

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 50 mg/mL

TargetMolReferences and Literature

1. Shannon-Lowe CD, et al. The effects of Maribavir on the autophosphorylation of ganciclovir resistant mutants of the cytomegalovirus UL97 protein. Herpesviridae. 2010 Dec 7;1(1):4. 2. Biron KK, et al. Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action. Antimicrob Agents Chemother. 2002 Aug;46(8):2365-72.

Related compound libraries

This product is contained In the following compound libraries:
Drug Repurposing Compound Library EMA Approved Drug Library Bioactive Compound Library Human Metabolite Library FDA-Approved & Pharmacopeia Drug Library Anti-Viral Compound Library Target-Focused Phenotypic Screening Library Orally Active Compound Library Anti-Infection Compound Library ReFRAME Related Library

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Keywords

Maribavir 176161-24-3 Microbiology/Virology Others Proteases/Proteasome HCV Protease inhibit BW1263W94 Cytomegalovirus CMV GW257406X Inhibitor Benzimidavir 1263W94 inhibitor

 

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