Modulation of hepatitis B virus CCCDNA transcription
AssigneesDrexel University, Baruch S. Blumberg Institute
InventorsJu-Tao Guo, Jinhong Chang, Timothy M. Block, William A. Kinney, Harold R. Almond
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Abstract
The present invention provides small molecule inhibitors of hepatitis B virus (HBV) covalently closed circular (ccc) DNA, which are useful as therapeutics in the management of chronic HBV. The compounds of the invention achieve epigenetic modification of the cccDNA, histone modification and histone deacetylase activity inhibition, thus modulating HBV cccDNA. The present invention further provides methods for modulating HBV cccDNA, for treating or preventing HBV in a subject, and for modulating cccDNA transcription of hepatitis B in a subject.
Claims15
A method of inhibiting covalently closed circular DNA (cccDNA) transcription of hepatitis B virus in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of class I histone deacetylase activity, wherein the inhibitor of class I histone deacetylase activity is selected from the group consisting of Trichostatin A, suberoyl bis hydroxamic acid, 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl] benzamide, and Apicidin or an analog thereof, or a stereoisomer or pharmaceutically acceptable salt thereof.
A method of treating hepatitis B in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of class I histone deacetylase activity, wherein the inhibitor of class I histone deacetylase activity is selected from the group consisting of Trichostatin A, suberoyl bis hydroxamic acid, 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl] benzamide, and Apicidin or an analog thereof, or a stereoisomer or pharmaceutically acceptable salt thereof.
A method of repressing hepatitis B virus covalently closed circular DNA, the method comprising contacting a hepatitis B virus with an inhibitor of class I histone deacetylase activity, wherein the inhibitor of class I histone deacetylase activity is selected from the group consisting of Trichostatin A, suberoyl bis hydroxamic acid, 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl] benzamide, and Apicidin or an analog thereof, or a stereoisomer or pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.