Maribavir

Modify Date: 2024-01-06 11:51:44

Maribavir Structure
Maribavir structure
Common Name Maribavir
CAS Number 176161-24-3 Molecular Weight 376.235
Density 1.7±0.1 g/cm3 Boiling Point 611.0±65.0 °C at 760 mmHg
Molecular Formula C15H19Cl2N3O4 Melting Point N/A
MSDS N/A Flash Point 323.3±34.3 °C

 Use of Maribavir


Maribavir is a potent inhibitor of histone phosphorylation catalyzed by wild-type pUL97 in vitro, with an IC50 of 3 nM. Maribavir has potent antiviral activity against HCMV and Epstein-Barr virus (EBV).

 Names

Name (2S,3S,4R,5S)-2-[5,6-dichloro-2-(propan-2-ylamino)benzimidazol-1-yl]-5-(hydroxymethyl)oxolane-3,4-diol
Synonym More Synonyms

 Maribavir Biological Activity

Description Maribavir is a potent inhibitor of histone phosphorylation catalyzed by wild-type pUL97 in vitro, with an IC50 of 3 nM. Maribavir has potent antiviral activity against HCMV and Epstein-Barr virus (EBV).
Related Catalog
Target

HCMV[1]

In Vitro Maribavir is a potent inhibitor of the autophosporylation of the wild type and all the major Ganciclovir (GCV) resistant UL97 mutants analysed with a mean IC50 of 35 nM. The M460I mutation results in hypersensitivity to Maribavir with an IC50 of 4.8 nM. A Maribavir resistant mutant of UL97 (L397R) is functionally compromised as both a Ganciclovir kinase and a protein kinase (~ 10% of wild type levels). Enzyme kinetic experiments demonstrate that Maribavir is a competitive inhibitor of ATP with a Ki of 10 nM[1]. Maribavir (1263W94) inhibits viral replication in a dose-dependent manner, with IC50 of 0.12±0.01 μM as measured by a multicycle DNA hybridization assay. The pUL97 protein kinase is strongly inhibited by Maribavir, with 50% inhibition occurring at 3 nM[2].
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 Assay 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].
References

[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.

 Chemical & Physical Properties

Density 1.7±0.1 g/cm3
Boiling Point 611.0±65.0 °C at 760 mmHg
Molecular Formula C15H19Cl2N3O4
Molecular Weight 376.235
Flash Point 323.3±34.3 °C
Exact Mass 375.075256
PSA 99.77000
LogP 2.71
Vapour Pressure 0.0±1.8 mmHg at 25°C
Index of Refraction 1.703
Storage condition 2-8℃

 Synonyms

5,6-Dichloro-N-isopropyl-1-(β-L-ribofuranosyl)-1H-benzimidazol-2-amine
1263W94
Camvia
BW 1263W94
5,6-Dichloro-2-(isopropyl)amino-1-(b-L-ribofuranosyl)benzimidazole
1263 W94
5,6-Dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole
(2S,3S,4R,5S)-2-(5,6-dichloro-2-(isopropylamino)-1H-benzo[d]imidazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
1H-Benzimidazol-2-amine, 5,6-dichloro-N-(1-methylethyl)-1-β-L-ribofuranosyl-
5,6-dichloro-N-(propan-2-yl)-1-(β-L-ribofuranosyl)-1H-benzimidazol-2-amine
Camvia (TN)
5,6-Dichloro-N-(1-methylethyl)-1-β-L-ribofuranosyl-1H-benzimidazol-2-amine
ntbc
5,6-Dichloro-N-isopropyl-1-b-L-ribofuranosyl-1H-benzimidazol-2-amine
Maribavir
Camvia(TM)
Bzurea
Benzimidavir